Bio Physics

A Primer On Excitable Nerve Cells
We are all made of the same stuff, Dewey.
Jim Peterson
Department of Mathematical Sciences
Clemson University
email: petersj@clemson.edu
May 23, 2006

Notes on Excitable Nerve Cells by James Peterson
Based On:
Notes On Neural Objects 1994 - 1995
Notes on Chained Neural Objects 1996
Notes on CMAC Neural Objects 1996
Class Notes: MTH SC 982 Spring 1997
Class Notes: MTH SC 450, MTH SC 827 Fall 2001
Research Notes: Air Force Rome IFSB, Summer 2005
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Contents
I Introductory Matter 9
1 Biological Information Processing 11
II Basic BioPhysics and Cellular Modeling 15
2 Some Chemistry Background: 17
2.1 Molecular Bonds: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2.2 Bond Comparisons: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
2.3 Energy Considerations: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
2.4 Hydrocarbons: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
3 Amino Acids: 27
3.1 Peptide Bonds: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
3.2 Chains of Amino Acids: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
4 Nucleic Acids 47
4.1 Sugars: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
4.2 Nucleotides: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
4.3 Complementary Base Pairing: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
4.4 A Quick Look at How Proteins Are Made: . . . . . . . . . . . . . . . . . . . . . . . 58
5 Cell Membranes and Ion Movement: 63
5.1 Membranes in Cells: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
3
5.2 The Physical Laws of Ion Movement: . . . . . . . . . . . . . . . . . . . . . . . . . 66
5.2.1 Ficke’s law of Diffusion: . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
5.2.2 Ohm’s Law of Drift: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
5.2.3 Einstein’s Relation: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
5.2.4 Space Charge Neutrality: . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
5.2.5 Ions, Volts and a Simple Cell: . . . . . . . . . . . . . . . . . . . . . . . . . 70
5.3 The Nernst - Planck Equation: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
5.4 Equilibrium Conditions: The Nernst Equation: . . . . . . . . . . . . . . . . . . . . . 74
5.4.1 An Example: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
5.5 One Ion Nernst Computations in MatLab: . . . . . . . . . . . . . . . . . . . . . . . 78
5.5.1 Exercises: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
6 Electrical Signaling: 83
6.1 The Cell Prior to KCl Disassociation: . . . . . . . . . . . . . . . . . . . . . . . . . 83
6.2 The Cell With K + Gates: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
6.2.1 The Cell With Outer KCl Reduced: . . . . . . . . . . . . . . . . . . . . . . 85
6.3 The Cell With NaCl Inside and Outside Changes: . . . . . . . . . . . . . . . . . . . 86
6.4 The Cell with N a+ Gates: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
6.5 The Nernst Equation For Two Ions: . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
6.6 The Nernst Equation For More Than Two Ions: . . . . . . . . . . . . . . . . . . . . 90
6.7 Multiple Ion Nernst Computations in MatLab: . . . . . . . . . . . . . . . . . . . . . 92
7 Transport Mechanisms: 95
7.1 Transport Mechanisms: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
7.1.1 Ion Channels: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
7.1.2 Passive Ion Transport: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
7.1.3 Active Transport Using Pumps: . . . . . . . . . . . . . . . . . . . . . . . . 103
7.1.4 A Simple Compartment Model: . . . . . . . . . . . . . . . . . . . . . . . . 103
4
8 Movement of Ions Across Biological Membranes: 111
8.1 Membrane Permeability: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
8.2 The Goldman-Hodgkin-Katz (GHK) Model: . . . . . . . . . . . . . . . . . . . . . . 116
8.3 The GHK Voltage Equation: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
8.3.1 Examples: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
8.4 The Effects of an Electrogenic Pump: . . . . . . . . . . . . . . . . . . . . . . . . . 128
8.5 Excitable Cells: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
9 Lumped and Distributed Cell Models 141
9.1 Modeling Radial Current: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142
9.2 Modeling Resistance: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
9.3 Longitudinal Properties: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145
9.4 Current in a Cable with a Thin Wall: . . . . . . . . . . . . . . . . . . . . . . . . . . 147
10 The Cable Model: 153
10.1 The Core Conductor Model Assumptions: . . . . . . . . . . . . . . . . . . . . . . . 154
10.2 Building the Core Conductor Model: . . . . . . . . . . . . . . . . . . . . . . . . . . 157
11 The Transient Cable Equations: 165
11.1 Deriving the Transient Cable Equation: . . . . . . . . . . . . . . . . . . . . . . . . 166
11.2 The Space and Time Constant of a Cable: . . . . . . . . . . . . . . . . . . . . . . . 169
12 Time Independent Solutions to the Cable Equation: 173
12.1 The Infinite Cable: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173
12.2 Solving the Time Independent Infinite Cable Equation: . . . . . . . . . . . . . . . . 174
12.2.1 Solving the Homogeneous Equation: . . . . . . . . . . . . . . . . . . . . . 176
12.2.2 Solving the Non-homogeneous Equation: . . . . . . . . . . . . . . . . . . . 177
12.3 Modeling Current Injections: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
12.4 Modeling Instantaneous Current Injections: . . . . . . . . . . . . . . . . . . . . . . 185
12.4.1 What Happens Away from 0? . . . . . . . . . . . . . . . . . . . . . . . . . 186
12.4.2 What Happens at Zero? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
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12.5 Idealized Impulse Currents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190
12.6 The Inner and Outer Current Solutions: . . . . . . . . . . . . . . . . . . . . . . . . 193
12.7 The Inner and Outer Voltage Solutions: . . . . . . . . . . . . . . . . . . . . . . . . 198
12.8 Summarizing The Infinite Cable Solutions: . . . . . . . . . . . . . . . . . . . . . . 199
12.9 Normalized Solutions: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200
12.10Some MatLab Implementations: . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203
12.10.1 Runtime Results: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205
12.10.2 Exercises: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 206
13 The Finite and Half-Infinite Space Cable 209
13.1 The Half-Infinite Cable Solution: . . . . . . . . . . . . . . . . . . . . . . . . . . . . 210
13.2 The Finite Cable Solution: Current Initialization: . . . . . . . . . . . . . . . . . . . 213
13.2.1 Parametric Studies: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220
13.2.2 Some MatLab Implementations: . . . . . . . . . . . . . . . . . . . . . . . . 221
13.2.3 Run-Time Results: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
13.2.4 Exercises: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224
13.3 The Finite Cable: Voltage Initialization: . . . . . . . . . . . . . . . . . . . . . . . . 226
13.3.1 Exercises: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229
13.4 Synaptic Currents: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 230
13.4.1 A Single Impulse: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232
13.4.2 Forcing Continuity in the Model: . . . . . . . . . . . . . . . . . . . . . . . 234
13.4.3 The Limiting Solution: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 236
13.4.4 Satisfying the Boundary Conditions: . . . . . . . . . . . . . . . . . . . . . . 238
13.4.5 Some Results: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240
13.5 Implications: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241
14 Simplified Dendrite - Soma - Axon Information Processing 245
14.1 A Simple Model of a Dendrite: The Core Conductor Model: . . . . . . . . . . . . . 248
14.2 Solutions to the Cable Model: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253
14.2.1 Time Independent Solutions: . . . . . . . . . . . . . . . . . . . . . . . . . . 253
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14.2.2 Time Dependent Solutions: . . . . . . . . . . . . . . . . . . . . . . . . . . . 256
14.3 The Ball and Stick Model: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 260
14.4 Simplifying Dendritic Arbors: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 264
15 The Diffusion Equation: 271
15.1 The Microscopic Space-Time Evolution of a Particle: . . . . . . . . . . . . . . . . . 273
15.2 The Random Walk And The Binomial Distribution: . . . . . . . . . . . . . . . . . . 276
15.3 Rightward Movement Has Probability 0.5 Or Less: . . . . . . . . . . . . . . . . . . 277
15.3.1 Finding The Average Of The Particles Distribution In Space And Time: . . . 278
15.3.2 Finding The Standard Deviation Of The Particles Distribution In Space And
Time: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280
15.3.3 Specializing To An Equal Probability Left And Right Random Walk: . . . . 282
15.4 Macroscopic Scale: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283
15.5 Leftward Movement Has Probability 0.5 Or Less: . . . . . . . . . . . . . . . . . . . 285
15.6 Obtaining The Probability Density Function: . . . . . . . . . . . . . . . . . . . . . . 286
15.6.1 Special Cases: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 288
15.7 Understanding The Probability Distribution Of The Particle: . . . . . . . . . . . . . 289
16 The Time Dependent Cable Solution: 291
16.1 The Solution For A Current Impulse: . . . . . . . . . . . . . . . . . . . . . . . . . . 292
16.1.1 Modeling The Current Pulses: . . . . . . . . . . . . . . . . . . . . . . . . . 292
16.1.2 Scaling the Cable Equation: . . . . . . . . . . . . . . . . . . . . . . . . . . 294
16.1.3 Applying the Laplace Transform In Time: . . . . . . . . . . . . . . . . . . . 295
16.1.4 Applying the Fourier Transform In Space: . . . . . . . . . . . . . . . . . . . 297
16.1.5 The T Transform Of the Pulse: . . . . . . . . . . . . . . . . . . . . . . . . 299
16.1.6 The Idealized Impulse T Transform Solution: . . . . . . . . . . . . . . . . . 300
16.1.7 Inverting The T Transform Solution: . . . . . . . . . . . . . . . . . . . . . 301
16.1.8 A Few Computed Results: . . . . . . . . . . . . . . . . . . . . . . . . . . . 304
16.1.9 Reinterpretation In Terms of Charge: . . . . . . . . . . . . . . . . . . . . . 304
16.2 The Solution To A Constant Current: . . . . . . . . . . . . . . . . . . . . . . . . . . 306
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17 The Basic Hodgkin - Huxley Model: 309

17.1 The Voltage Clamped Protocol: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313
17.2 The Hodgkin - Huxley Gate Model: . . . . . . . . . . . . . . . . . . . . . . . . . . 314
17.2.1 Activation and Inactivation Variables: . . . . . . . . . . . . . . . . . . . . . 317
17.3 The Hodgkin-Huxley Sodium and Potassium Model: . . . . . . . . . . . . . . . . . 318
17.4 The Hodgkin - Huxley Model Solution Under The Voltage Clamp Protocol: . . . . . 321
17.4.1 Encoding The Dynamics: . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321
17.5 Computing the Solution: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
17.6 Hodgkin - Huxley C++ Simulation Code: . . . . . . . . . . . . . . . . . . . . . . . 326
17.6.1 function.c: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326
17.6.2 rest.c: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331
17.6.3 run plot.c: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 336
17.6.4 rkf5 plot.c: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 340
17.6.5 C++ Code: The Run-Time Code: . . . . . . . . . . . . . . . . . . . . . . . 347
17.6.6 The Development of An Action Potential: . . . . . . . . . . . . . . . . . . . 352
17.7 Hodgkin - Huxley Matlab Simulation Code: . . . . . . . . . . . . . . . . . . . . . . 358
17.7.1 SolveSimpleHH.m . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 358
17.7.2 The Hodgkin - Huxley Dynamics: . . . . . . . . . . . . . . . . . . . . . . . 359
17.7.3 Modifications to The Built In Runga - Kutte Function: . . . . . . . . . . . . 366
17.7.4 RunTime Results: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 367
17.7.5 Exercise: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 372
17.8 Setting Up A Large C++ Simulation Study: . . . . . . . . . . . . . . . . . . . . . . 373
17.8.1 C++ Code: The Run-Time Code: . . . . . . . . . . . . . . . . . . . . . . . 375
17.8.2 Analyzing the Parametric Study Results: . . . . . . . . . . . . . . . . . . . 377
17.8.3 Computing the Average Simulation Data: . . . . . . . . . . . . . . . . . . . 379
III References 387
Bibliography 389
8
Part I
Introductory Matter
9
Chapter 1
Biological Information Processing
We have written these notes to help you if you, like us, are well trained in mathematics, but want to
learn some of the basic principles of chemistry, biology and neuroscience that underlie the study of
biological information processing. Perhaps you also wish to develop software models of cognition or
learn better the material that underlies detailed mathematical models of neurons and other biological
cells. We have written these notes over a period of years as a way of remembering the things we have
studied and also as a way to make cross connections to other areas of intellectual discourse. Our son,
Quinn, helped us by designing some of the graphics so this has been a family undertaking.
We have have done a fair bit of reading and study to prepare ourselves for necessary abstractions
we need to make in our journey. We have learned a lot from various studies of theoretical biology
and computation and so forth. You will need to make this journey too so to help you here are some
specific comments about the sources we have learned much from:
Basic Physiology:
It is clear that the regulation of information processing depends on many agents. These can
be hormones and multiple neurotransmitters all interacting on vastly different time scales in
mutually dependent ways. It is important to gain an overview understanding of these areas. The
references below were how we have gotten started in this process:
• Animal physiology in Eckert (Eckert et al. (3) 1998) .
• General Neurobiology in Hall (Hall (5) 1992) .
11
• Ion Channels in Hille (Hille (6) 1992) .
• Neuropharmacology in Stone (Stone (11) 1995) .
• Endrocrinology in Hadley (Hadley (4) 1996) .
• Immunology in Austyn (Austyn and Wood (1) 1993) .
We are going to explore some of ideas in Biological Information Processing via excitable nerve
cells. We find that a lot of this material is difficult to find in an accessible form. There are
parts of this area that are slanted heavily towards computer science and software engineering;
other parts towards physics and chemistry; and, of course, other parts towards various areas of
biology. In particular, we have found the following references really useful:
Basic Cellular Physiology:
• In Ionic Channels of Excitable Membranes by Hille (Hille (6) 1992) , we see a great
book on ion channels in general and in ”Classical Biophysics of the Squid Giant Axon”
(Hille (7) 1992) , we see a particular chapter devoted to the biophysics of the squid axonal
fiber.
• The book Foundations of Cellular Neurophysiology by Johnston and Wu (Johnston and

Wu (8) 1995) , is a detailed reference to cellular physiology. In ”Hodgkin and Huxley’s
Analysis of the Squid Giant Axon” (Johnston and Wu (9) 1995) , we note the particular
chapter devoted to the Hodgkin and Huxley analysis of the giant squid axon.
• The chapter ”Multiple Channels and Calcium Dynamics”, in Methods of Neuronal Mod-
eling edited by Koch and Segev (Yamada et al. (15) 1987) is a reference to a very detailed
mathematical model for the generation of the output pulse of a neuron that does include
second messenger effects. Although quite old, it is still very useful to read.
• The two volumes of Cellular Biophysics, Volume 1, Transport and Volume 2, Electrical
Properties, (Weiss, Weiss (12, 13) 1996, 1996) give a thorough treatment of this area. In
the chapter ”The Hodgkin - Huxley Model” in Volume 2 (Weiss (14) 1996) ), we reference
a particular treatment of the Hodgkin - Huxley models.
12
To model these things, we can use the Genesis modeling language as discussed in The Book of
Genesis: Exploring Realistic Neural Models with the GEneral NEural SImulation System,
by Bower and Beeman (Bower and Beeman (2) 1998) or home grown code written in C++ or
MatLab.
13
14
Part II
Basic BioPhysics and Cellular Modeling
15
Chapter 2
Some Chemistry Background:
We will begin by going through some background material on what might be called the chemistry
of life; we had a hard time getting all of these things straight, so for all of those mathematician and
computer scientist types out there, here is the introduction we wished we had when we started out.
Molecules depend on the interplay of non covalent and covalent interactions. Recall covalent
bonds share electrons in a tightly coupled way. There are three fundamental covalent bonds:
• Electrostatic Bonds due to Coulomb’s Law
• Hydrogen Bonds
• Vanderwaals Bonds
2.1 Molecular Bonds:
The force F between two charges is given by the formula:
1 q1 q2
F = (2.1)
4π0 r2
where q1 and q2 are the charges on the bonding units, r is the distance between the units and 0 is a
basic constant which depends on the solution (air, water and so forth) that the units live within. For
17
(a) Electrostatic Attraction Between Two (b) Typical Hydrogen Bonds

Molecules
Figure 2.1: Types of Bonding
Example Bond Length

O-H· · ·O 2.70 Å
O-H· · ·O− 2.63 Å
O-H· · ·N 2.88 Å
N-H· · ·O 3.04 Å
N+ -H· · ·O 2.93 Å
N-H· · ·N 3.10 Å
Table 2.1: Hydrogen Bond Lengths
example, in Figure 2.1(a), we see a representation of the electrostatic attraction between two common
molecules; one with a carboxyl and the other with an amide group on their ends.
Hydrogen Bonds occur when a hydrogen atom is shared between two other atoms as shown in
Figure 2.1(b): The atom to which the hydrogen is held more tightly is called the hydrogen donor
and the other one which is less tightly linked is called the hydrogen acceptor. You can see this
represented abstractly as follows:
H Donor Length H Acceptor

−O − H− 2.88Å · · · − N−
−N − H− 3.04Å · · · − O−
Recall, one Angstrom, Åis 10−10 meters or 10−8 cm. Hydrogen bond lengths vary as we can see in
Table 2.1:
The donor in biological systems is an oxygen or nitrogen with a covalently attached hydrogen.
18
(a) Typical Hydrogen Bonds In A Helix (b) Vanderwaals Forces Between

Structure Molecules
Figure 2.2: Bonds Due to Hydrogen Sharing or Attraction
The acceptor is either oxygen or nitrogen. These bonds are highly directional. The strongest bonds
occur when all the atoms line up or are collinear (think alignment of the planets like in the Tomb
Raider movie!). In Figure 2.2(a), we see an idealized helix structure with two attached carbon groups.
The carbons are part of the helix backbone and the rest of the molecular group spills out from the
backbone. If the two groups are separated enough along the background, the oxygen of the top one
is close enough physically to the nitrogen of the bottom group to allow them to share a hydrogen.
As you might expect, this sort of hydrogen bonding stabilizes helical structures. This sort of upward
spiral occurs in some protein configurations.
There is also a nonspecific attractive force which occurs when any two atoms are 3 to 4 Å apart
which is called a Vanderwaals Bond. The basis of this bond is that the charge distribution around an
atom is time dependent and at any instant is not perfectly symmetrical. This ”transient” asymmetry
in an atom encourages a similar asymmetry in the electron distribution around its neighboring atoms.
The standard picture of this force is shown in Figure 2.2(b). The distance for maximum attraction
varies with the atom involved as we can see in Table 2.2:
Table 2.2 shows us the H − C has a 3.20 Å Vanderwaals interaction radius; H − N has a 2.70 Å;
and H − P has a 13.10 Å.
19
Atom Radius of Maximum Attraction

H 1.20 Å
C 2.00 Å
N 1.50 Å
O 1.40 Å
S 1.85 Å
P 1.90 Å
Table 2.2: Maximum Attraction Distances
Bond Interaction Distance Bond Energy
Electrostatic 2.80 Å 3 - 7 kcal/mole
Hydrogen 2.70 - 3.10 Å 3 - 7 kcal/mole
Vanderwaals 2.70 - 3.20 Å 1 kcal/mole
Covalent 1.00 Å 80 kcal/mole
Table 2.3: Bond Distances by Type
2.2 Bond Comparisons:
These three different types of bonds are therefore ranked according to their interaction distance as
shown in Table 2.3:
where although we haven’t really discussed it, it should be easy to understand that to pull a bond
apart you would have to exert a force or in other words do some work. The amount of work you do
can be measure in many units, but a common one in biology is the calorie which can be converted to
the standard physics energy measure of ergs. The abbreviation kcal refers to 103 calories and the term
mole refers to a collection of 6.02 1023 (Avogadro’s Number) of molecules. Note that the covalent
bond is far stronger than the other bonds we have discussed!
2.3 Energy Considerations:
The ultimate source of energy for most life is the sun (we will neglect here those wonderful mid-
Atlantic smokers with a sulfur based life chemistry that does not require any oxygen or photosynthesis
at all). Energy can be stored in various ways for later use - kind of like a battery. Some common energy
sources are given in Table 2.4:
Basically, energy is moved from one storage source or another via special helper molecules so that
20
Source Energy Stored

Green Photon Energy 57 kcal/mole
ATP (Adenine Triphostate) 12 kcal/mole
(universal currency of biochemical energy)
Each vibrational degree of freedom in a 0.6kcal/mole at 25 degrees C
molecule
Covalent bond 80 kcal/mole
Table 2.4: Energy Sources
(a) A Water Molecule (b) Polar Bonding Without Water
Figure 2.3: Special Forces Act On Water
a living thing can perform its daily tasks of eating, growing, reproducing and so forth. Now for us, we
are going to concentrate on what happens inside a cell. Most of us already know that the inside of a
cell is a liquid solution which is mostly water but contains many ions. You probably have this picture
in your head of an ion, like N a+ sitting inside the water close to other such ions with which they can
interact. The reality is more complicated. Water is made up of two hydrogens and one oxygen and
is what is called a polar molecule. As you can see from Figure 2.3(a), the geometry of the molecule
means that the minus and plus charges are not equally balanced. Hence, there is a charge gradient
which we show with the vertical arrow in the figure. The asymmetrical distribution of charge in water
implies that water molecules have a high affinity for each other and so water will compete with other
ions for hydrogens to share in a hydrogen bond.
If we had two molecules, say N H3 and COH2 , shown in Figure 2.3(b), we would see a hydrogen
bond from between the oxygen of COH2 and the central hydrogen of N H3 due to the asymmetrical
distribution of charge in these molecules. However, in an environment with water, the polarized water
21
(a) Polar Bonding With Water (b) Ion Water Cages
Figure 2.4: The Polarity Of Water Induces Cages To Form
molecules are attracted to these asymmetrical charge distributions also and so each of these molecules
will actually be surrounded by a cage of water molecules as shown in Figure 2.4(a). This shield of
polar water molecules around the molecules markedly reduces the attraction between the + and −
sites of the molecules. The same thing is true for ionized molecules. If we denote a minus ion by a
triangle with a minus inside it and a plus ion by a square with a plus inside it, then this caging effect
would look something like what is shown in Figure 2.4(b).
This reduction occurs because the electric field of the shield opposes the electric field of the ion
and so weakens it. Consider common table salt, N aCl. This salt can ionize into N a+ and Cl− , the
exact amount that ionizes being dependent on the solution you drop the salt into. The minus side of
N aCl is very attractive to the positive side of a polar water molecule which in turn is attracted to the
negative side of another water molecule. The same thing can be said about the positive side of the salt.
The presence of the polar water molecules actively encourages the splitting or disassociating of the
salt into two charged pieces. Hence, water can dissolve many polar molecules, like the salt mentioned
above, that serve as fuels, building blocks, catalysts and information carriers. This causes a problem
because the caging of an ion by water molecules also inhibits ion interactions. Biological systems
have solved this problem by creating water free micro environments where polar interactions have
maximal strength. A consequence of this is that non polar groups aren’t split apart by water and so
it is energetically more favorable for non polar molecules to be placed into one cage rather that have
a separate water cage for each one. If we denote a non polar molecule by the symbol N P enclosed
in a circle, as a thought experiment we can add our non polar molecule to a water environment. A
22
(a) Non Polar (b) Non Polar Molecule Group Wa-

Molecule Water ter Cages
Cages
Figure 2.5: It Is More Efficient To Group Non polar Molecules In Cages
cavity in the water is created because the non polar molecule disrupts some hydrogen bonds of water
to itself. We see a picture like the one in Figure 2.5(a). This means that the number of ways to from
hydrogen bonds in the cage around the non polar molecule is smaller that the the number of ways to
from hydrogen bonds without the non polar molecule present. This implies a cost to caging N P as
order is created. Now if a second non polar molecule N P is added, where will it go? If a second
cage is created, more hydrogen bonds are used up than if both N P molecules clump together inside
one cage. Remember always that order is costly and disorder is energetically favored. So two non
polar molecules clump together to give the picture shown in Figure 2.5(b)
2.4 Hydrocarbons:
We need to learn a bit about the interesting molecules we will see in our quest to build interesting
models of cell function. Any good organic chemistry book is good to have as a general reference on
your shelf if you really like this stuff. We will begin with simple hydrocarbons.
The basic thing to remember is that carbon’s outer shell of electrons is four shy of being filled up.
The far right edge of the periodic table consists of the noble gases or elements because their outer
most electron shells are completely populated. Hence, they are considered special or noble. For us,
23
(a) Methyl with Residue R (b) Ethyl with

Residue R
Figure 2.6: Methyl and Ethyl Can Have Side Chains of Arbitrary Complexity Called Residues
a quick way to understand hydrocarbons is to think of a carbon as wanting to add four more electrons
so that it can be like a noble gas. Of course, there are less anthropomorphic ways to look at it and
really nice physical models but looking at it in terms of a want really helps! We typically draw a
carbon atom, denoted by C, surrounded by four lines. Each of the lines is ninety degrees apart and
the lines represent a covalent bond with something. In Figure 2.6(a), we see a carbon with three of its
covalent bonds with hydrogen (hence, these lines go from the central C to an H) and the last covalent
bond on the left goes to an unknown molecule we denote as R. The R is called a residue and must
supply an electron for this last covalent bond. The molecule CH4 is called methyl and is the simplest
hydrocarbon (note the residue here is just a hydrogen); here we have the molecule by CH3 R; for
example, a ionized phosphate group, P O3− , would supply such an electron and we would have the
molecule CH3 P O3 . The CH3 R molecule is shown in Figure 2.6(a). The next simplest hydrocarbon
is one that is built from two carbons. If the two carbons bond with each other, that will leave six
bonds left over to fill. If all of these bonds are filled with hydrogens, we get the molecule ethyl with
chemical formulae C2 H6 . Usually, we think of the left most hydrogen as being replaced by a residue
R which we draw in Figure 2.6(b).
Clearly, these groupings can get complicated very quickly! We won’t show any more specific
molecules, but you can get the flavor of all this by looking at Figure 3.1 which shows a few of the
residues we will see attached to various hydrocarbons. Of course, we can also use more than two
carbons and if you think about it a bit, as the number of carbons we use goes up, there is no particular
reason to think our pictures will always organize the carbons in a central chain like beads on a string.
24
Instead, the carbons may forms side chains or branches, from circular groupings where the last carbon
in a group bonds to the first carbon and so forth. Also our pictures are just idealizations to help us think
about things; these molecules live in solutions, so there are water cages, there are three dimensional
concerns - like which carbons are in a particular plane - and so forth. We won’t really discuss those
things in a lot of detail. However, the next step is to look at a special class of molecules called amino
acids and we will see some of this complication show up in our discussions there.
25
26
Chapter 3
Amino Acids:
An α amino acid consists of the following things:
• an amino group N H2
• a carbonyl group COOH
• a hydrogen atom H
• a distinctive residue R
We can see how a molecule of this type will be assembled using are simple pictorial representation
of covalent bonds. In Figure 3.3(a), we see a typical amino acid using the building blocks we have
mentioned. Now think of the central carbon as the α carbon so that we distinguish it from any other
carbons that are attached to it. As we have mentioned, a carbon lacks four electrons in its outer shell
so it is energetically favorable to seek alliances with other molecules so that it can fill these empty
spots. This is, of course, a very anthropomorphic way to look at it, but it helps you see what is going
on at a gut level. So draw the α carbon with four dots around it. These are the places in the outer shell
that are not filled. Chemical theory tells us that the outer shell of a carbon consists of four groupings
of two electrons each. So when we draw four groupings of just one electron per group we are clearly
indicating that one electron is missing in each group. Now the amide molecule is handled in a similar
way: the nitrogen is missing three electrons in its outer shell which we indicate by three single dots
placed around the nitrogen. A hydrogen has only one electron as it has a very simple shell structure;
27
Figure 3.1: Common Residues
28
hence it is drawn as a single dot. So hydrogen would like one more electron to fill its outer shell
and the nitrogen would also like an additional electron to fill one of its groups. So a good solution
is for the two atoms to share an electron which we denote by a box around the two single electrons.
Continuing in this way, we can build an electron dot diagram for the amide and its connection to the
α carbon. The carbonyl is a little more complicated. So far we have only looked at bonds between
atoms where one electron is shared. Another type of bond which is even stronger is one where two
of the outer shell electrons are shared between two atoms. The carbonyl group would be written as
C = OOH to reflect the fact the there is such a double bond between the carbon and the first oxygen.
Oxygen is missing only two electrons in its outer shell and so this double bond which is indicated
by the double bars = completely fills the outer shell of the oxygen and half of the outer shell of the
carbon. One of the remaining two outer shell groups is then filled by a hydroxyl group, OH. Note the
hydroxyl group is an oxygen with one of its outer shell groups filled by a hydrogen leaving one group
to fill. It does this by sharing with one of the remaining two groups that are open on the carbon of the
carbonyl group. This leaves one opening left on the carbon of the carbonyl which is used to make a
shared bond with the α carbon of the amino acid.
The entire electron dot diagram is shown in Figure 3.2 and it is very complex. So we generally do
not use this kind of explicit notation to draw an amino acid. All of this detail is assumed in the simple
skeleton formula we see in Figure 3.3(a) and in the notation CH2 N H2 COOH.
An amino acid can exist in ionized or non ionized forms as shown in Figure 3.3(b) and of course
all we have said about water cages is still relevant.
Another important thing is the three dimensional (3D) configuration of an amino acid. The L-form
is shown in Figure 3.4(a) and the R-form is shown in Figure 3.4(b).
In the L-form, the α carbon, Cα , comes out of the page. To see this, take your right hand, line
up the fingers along the N H2 line and rotate your fingers left towards R. Note your thumb points out
of the page. This is called the L-form because you rotate left. If you switch the position of the amide
and carbonyl group you get the R-form. Now line your fingers along the N H2 line again so that you
can curl them naturally towards the R group. Note you can’t do this unless you let your thumb point
into the page. So here, we have Cα going into the page. For unknown reasons, only L-forms are used
in life on earth.
29
Figure 3.2: A Sample Amino Acid with Electron Shells
(a) A Sample Amino Acid (b) Amino Acid Forms
Figure 3.3: Amino Acid Structure
30
(a) L-form of an Amino Acid (b) R-form of an Amino Acid
Figure 3.4: Three Dimensional Configuration Of Amino Acids
Now there are a total of twenty amino acids: we list them in Figure 3.5(glycine, alanine, valine
and leucine), Figure 3.6 (isoleucine, proline and phenylalanine), Figure 3.7 (tyrosine, tryptophan
and cysteine), Figure 3.8 (methionine, serine and lysine), Figure 3.9 (threonine, arginine, histidine
and aspartate) and Figure 3.10 (glutamate, asparagine and glutamine). As you can see, all have the
common amino acid structure with different residues R attached. The type of residue R determines the
chemical and optical reactivity of the amino acids. For convenience, we list the standard abbreviations
for the names of the amino acids in table form as well as in the figures in Table 3.1.
3.1 Peptide Bonds:
Amino acids can link up in chains because the COOH on one can bond with the N H2 on another as
is seen in Figure 3.11(a). In this figure, there is an outlined box that contains the bond between the
COOH and the N H2 ; this is called the peptide bond and is shown again in Figure 3.11(b).
In Figure 3.11(a), R1 is the residue or side chain for the first amino acid and R2 is the side chain
for the other. Recall, the central carbon in the amino acid is labeled the α carbon. The important
characteristic about the peptide bond is that the grouping shown in Figure 3.12(a) forms a rigid two
31
Figure 3.5: Amino Acids: 1 - 4
32
33
34
35
36
37
Amino Acid Abbreviation

Glycine G, Gly
Alanine A, Ala
Valine V, Val
Leucine L, Leu
Isoleucine I, Ile
Proline P, Pro
Phenylalanine F, Phe
Tyrosine Y, Tyr
Tryptophan W, Trp
Cysteine C, Cys
Methionine M, Met
Serine S, Ser
Lysine K, Lys
Threonine T, Thr
Arginine R, Arg
Histidine H, His
Aspartate D, Asp
Glutamate E, Glu
Asparagine N, Asn
Glutamine G, Gln
Table 3.1: Abbreviations for the Amino Acids
(a) The Bond Between Two Amino Acids (b) The Peptide Bond
Figure 3.11: Bonds Between Amino Acids
38
(a) The Peptide Bond Plane (b) A Three Amino Acid Chain
Figure 3.12: Amino Acid Bond Into Chains
dimensional plane. The peptide bond allows amino acids to link into chains as is shown in Figure
3.12(b). In this picture there are two peptide bonds which are shaded and three amino acids.
If you look at the shaded boxes that represent the peptide bonds, it isn’t hard to imagine that these
two boxes could rotate or spin about the Cα to Cα axes you see. This is indeed true and the best way
to see it is to add the actual detail of the peptide bond to the boxes. In the first box, there is a N − Cα
axis and in the second box, there is a Cα − C axis. These two axes have a common center at the
central Cα carbon of the amino acid chain. We have tried to represent this in Figure 3.13(a) in which
we show the two axes in question. Then in Figure 3.13(b)
we show that the first box can be rotated Φ degrees about the N − Cα axis and the second box
can be rotated by Ψ degrees about the Cα − C axis. You can see that the side chains, R1 , R2 and R3 ,
then hang off of this chain of linked peptide bonds. A longer chain is shown in Figure 3.14. In this
long chain, there are two rotational degrees of freedom at the central carbon of any two peptide bonds.
This means that if we imagine the linked peptide bonds as beads on a string, there is a great deal of
flexibility possible in the three dimensional configuration of these beads on the string. It isn’t hard to
imagine that if the beads of string were long enough, full loops could form and there could even be
39
(a) Details of the Peptide Bonds in a Chain (b) The Peptide Bond Axis Rotations
Figure 3.13: Peptide Bond Details
complicated repeated patterns or motifs. Also, these beads on a string are molecular groupings that
are inside a solution that is full of various charged groups and the residues or side chains coming off
of the string are also potentially charged. Hence, there are many forces that act on this string including
hydrogen bonds between residues, Vanderwaals forces acting on motifs and so forth.
If we look at one three amino acid piece of a long chain, we would see the following molecular
form as represented in Figure 3.15.
As discussed above, as more and more amino acids link up, we get a chain of peptide bonds whose
geometry is very complicated in solution. To get a handle on this kind of chain at a high level, we
need to abstract out of this a simpler representation. In Figure 3.16, we show how we can first drop
most of the molecular detail and just label the peptide bond planes using the letter P.
We see we can now represent our chain in the very compact form −N CCN CCN CCN −. This
is called the backbone of the chain. The molecules such as side chains and hydrogen atoms hang off
the backbone in the form that is most energetically favorable. Of course, this representation does not
show the particular amino acids in the chain, so another representation for a five amino acid chain
would be A1 A2 A3 A4 A5 where the symbol Ai for appropriate indices i represents one of the twenty
amino acids. The peptide bonds are not even mentioned as it is assumed that they are there. Also,
note that in these amino acid chains, the left end is an amino group and the right end is a carbonyl
group.
40
Figure 3.14: A Five Amino Acid Chain
Figure 3.15: Molecular Details of a Chain
41
Figure 3.16: A First Chain Abstraction
3.2 Chains of Amino Acids:
We roughly classify chains of amino acids by their length. Hence, we say
• polypeptides are chains of amino acids less than or equal to 50 units long. Clearly, this naming
is a judgment call.
• longer chains of amino acids are called proteins
As we mentioned earlier, these long chains have side chains and other things that interact via
weak bonds or via other sorts of special bonds. For example, the amino acid cysteine (see Figure
3.7) has the residue CH2 SH and if the residues of two cysteine’s in an amino acid chain can become
physically close (this can happen even if the two cysteines are very far apart on the chain because the
chain twists and bend in three dimensional space!), a S − S bond can form between the sulphur in
the SH groups. This is called a disulfide bond and it is yet another important bond for amino acid
chains. An example of this bond occurs in the protein insulin as shown in Figure 3.17.
In Figure 3.17, note we represent the amino acid chains by drawing them as beads on a string:
each bead is a circle containing the abbreviation of an amino acid as we listed in Table 3.1. This is a
very convenient representation even if much detail is hidden. In general, for a protein, there are four
ways to look at its structure:
• the primary structure is the sequence of amino acids in the chain as shown in Figure 3.18. To
know this, we need to know the order in which the amino acids occur in the chain: this is called
sequencing the protein.
42
Figure 3.17: Disulfide Insulin Protein
Figure 3.18: Primary Structure of a Protein
• Due to amino acid interactions along the chain, different regions of the full primary chain may
form local three dimensional structures. If we can determine these, we can say we know the
secondary structure of the protein. An example is a helix structure as shown in Figure 3.19.
• If we pack secondary structures into one or more compact globular units called domains, we
obtain the tertiary structure an example of which is shown in Figure 3.20. In this figure, each
rectangle represents secondary structural elements.
• Finally, the protein my contain several tertiary elements which are organized into larger struc-
tures. This way the amino acid far apart in the primary sequence structure can be brought close
enough together in three dimensions to interact. This is called the quatenary structure of the
protein. An example is shown in Figure 3.21
43
Figure 3.19: Secondary Structure of a Protein
44
Figure 3.20: Tertiary Structure of a Protein
Figure 3.21: Quatenary Structure of a Protein
45
46
Chapter 4
Nucleic Acids
Our genetic code is contained in linear chains of what are called nucleic acids in combination with a
particular type of sugar. These nucleic acid plus sugar groups are used in a very specific way to code
for each of the twenty amino acids we mentioned in Chapter 3. So our next task is to discuss sugars
and nucleic acids and the way these things are used to code for the amino acids.
4.1 Sugars:
Consider the cyclic hydrocarbon shown in Figure 4.1(a) The ring you see in Figure 4.1(a) is formed
from five carbons and one oxygen. For sugars, we label the carbons with primes as 1 C 0 to 6 C 0
because it will be important to remember which side chains are attached to which carbons. This type
of structure is called a pyran and can be indicated more schematically as in Figure 4.1(b)
Another common type of structure is that shown in Figure 4.2(a) which is formed from four
carbons and one oxygen. We label the carbons in a similar fashion to the way we labeled in the pyran
molecule. More symbolically, we would draw a furan as shown in Figure 4.2(b).
We will spend most of our time with the furan structures which have the very particular three
dimensional geometry shown in Figure 4.3(a). Note that 3 C 0 and 5 C 0 are out of the plane formed by
O − 1 C 0 − 2 C 0 − 4 C 0 ; this is called the 3 C 0 endo form. Another three dimensional version of the furan
molecule is the 2 C 0 endo form shown in Figure 4.3(b)
Here, 2 C 0 and 5 C 0 are out of the plane formed by O − 1 C 0 − 3 C 0 − 4 C 0 . Looking ahead some, these
47
(a) Details of a Cyclic Hydrocar- (b) The Schematic for Pyran

bon Sugar: Pyran
Figure 4.1: The Pyran Structure
(a) Details of a Cyclic Hydrocar- (b) The Schematic for Furan

bon Sugar: Furan
Figure 4.2: The Furan Structure
48
(a) The 3 C 0 endo Furan (b) The 2 C 0 endo Furan
Figure 4.3: Three Dimensional Furan Structures
three dimensional forms are important because only certain ones are used in biologically relevant
structures. Later, we will define the large molecules DNA and RNA and we will find that DNA uses
the 2 C 0 endo and RNA, the 3 C 0 endo form. Now the particular sugar we are interested in is called
ribose which will come in an oxygenated and non-oxygenated (deoxy) form. Consider the formula
for a ribose sugar as shown in Figure 4.4(a). Note the 2 C 0 carbon has an hydroxyl group on it. If we
remove the oxygen from this hydroxyl, the resulting sugar is known as the deoxy-ribose sugar (see
Figure 4.4(b)).
4.2 Nucleotides:
There are four special nitrogenous bases which are important. They come in two flavors: purines and
pyrimidines. The purines have the form shown in Figure 4.5(a) while the pyrimidines have the one
shown in Figure 4.5(b).
There are two purines and two pyrimidines we need to know about: the purines adenine and
guanine and the pyrimidines thymine and cytosine. These are commonly abbreviated as shown in
Table 4.1:
There chemical formulae are important, so we show their respective forms in Figure 4.6(a) (Ade-
nine is a purine with an attached amide on 6 C 0 ), Figure 4.6(b) (Guanine is a purine with an attached
49
(a) The Ribose Sugar (b) The Deoxy Ribose Sugar
Figure 4.4: Oxygenated and De-oxygenated Ribose Sugars
(a) The Generic Purine (b) The Generic Pyrimidine
Figure 4.5: Forms Of Nitrogenous Bases
Type Name Abbreviation

Purine Adenine A
Purine Guanine G
Pyrimidine Thymine T
Pyrimidine Cytosine C
Table 4.1: Abbreviations for the Nitrogenous Bases
50
(a) Adenine (b) Guanine
Figure 4.6: Purine Nucleotides
oxygen on 6 C 0 ), Figure 4.7(b) (Cytosine is a pyrimidine with an attached amide on 4 C 0 ), and Figure
4.7(a) (Thymine is a pyrimidine with an attached oxygen on 4 C 0 ).
These four nitrogenous bases can bond to the ribose or deoxyribose sugars to create what are called
nucleotides. For example, adenine plus deoxyribose would give a compound called deoxy-adenoside
as shown in Figure 4.8.
In general, a sugar plus a purine or pyrimidine nitrogenous base give us a nucleoside. If we add
phosphate to the 5 C 0 of the sugar, we get a new molecule called a nucleotide (note the change from
side to tide!). In general, sugar plus phosphate plus nitrogenous base gives nucleotide. An example
is deoxy-adenotide as shown in Figure 4.9.
This level of detail is far more complicated and messy than we typically wish to show; hence, we
generally draw this in the compact form shown in Figure 4.10. There, we have replaced the base with
a simple shaded box and simply labeled the primed carbons with the numerical ranking. In Figure
4.11 we show how nucleotides can link up into chains: bond the 5 C 0 of the ribose on one nucleotide to
the 3 C 0 of the ribose on another nucleotide with a phosphate or P O3− bridge. Symbolically this looks
like Figure 4.11.
This chain of three nucleotides has a terminal OH on the 5 C 0 of the top sugar and a terminal OH
on the 3 C 0 of the bottom sugar. We often write this even more abstractly as shown in Figure 4.12.
or just OH− Base 3 P Base 2 P Base 1 P −OH, where the P denotes a phosphate bridge.
For example, for a chain with bases adenine, adenine, cytosine and guanine, we would write OH −
51
(a) Thymine (b) Cytosine
Figure 4.7: Pyrimidine Nucleotides
Figure 4.8: deoxy-adenoside
52
Figure 4.9: deoxy-adenotide
Figure 4.10: A General Nucleotide
53
Figure 4.11: A Nucleotide Chain
Figure 4.12: An Abstract Nucleotide Chain
54
Figure 4.13: The Tyrosine - Adenine Bond
Figure 4.14: The Cytosine - Guanine Bond
A − p − A − p − C − p − G − OH or OHApApCpGOH. Even this is cumbersome, so we will leave

out the common phosphate bridges and terminal hydroxyl groups and simply write AACG. It is thus
understood the left end is an OH terminated 5 C 0 and the right end an hydroxyl terminated 3 C 0 .
4.3 Complementary Base Pairing:
The last piece in this puzzle is the fact that the purine and pyrimidine nucleotides can bond together
in the following ways: A to T or T to A and C to G or G to C. We say that adenine and thymine
and cytosine and guanine are complementary nucleotides. This bonding occurs because hydrogen
bonds can form between the adjacent nitrogen or between adjacent nitrogen and oxygen atoms. For
example, look at the T − A bond in Figure 4.13. Note the bases are inside and the sugars outside.
Next, look at the C − G bond as shown in Figure 4.14.
55
Chain One Chain Two

5 3
end end
C G
T A
A T
C G
G C
G C
C G
T A
A T
T A
T A
C G
G C
3 5
end end
Table 4.2: Two Complimentary Nucleotide Chains
Figure 4.15: A Cross-section of a Nucleotide Helix
Now as we have said, nucleotides can link into a long chain via the phosphate bond. Each base in
this chain is attracted to a complimentary base. It is energetically favorable for two chains to form:
chain one and its complement chain 2. In Table 4.2, we see how this pairing is done for a short
sequence of nucleotides:
Note that the 5 pairs with a 3 and vice versa. In the table, each pair of complimentary nucleotides is
called a complimentary base pair. The forces that act on the residues of the nucleotides and between
the nucleotides themselves coupled with the rigid nature of the peptide bond between two nucleotides
induce the two chains to form a double helix structure under cellular conditions which in cross-section
(see Figure 4.15 ) has the bases inside and the sugars outside.
The complimentary nucleotides fit into the spiral most efficiently with 100 degrees of rotation and
56
(a) The Base-Base Pair Rotation (b) The Nucleotide Uracil
Figure 4.16: Helix Base Pair Rotation And RNA Substitution Uracil
1.5 Angstroms of rise between each base pair. Thus, there are 3.6 base pairs for every 360 degrees of
rotation around the spiral with a rise of 3.6 × 1.5 = 5.4 Angstroms. This is, of course, hard to draw!
If you were looking down at the spiral from the top, you could imagine each base to base pair as a set
of bricks. You would see a lower set of bricks and then the next pair of bricks above that pair would be
rotated 100 degrees as shown in Figurebricks. To make it easier to see what is going on, only the top
pair of bases have the attached sugars drawn in. You can see that when you look down at this spiral,
all the sugars are sticking outwards. The double helix is called DNA when deoxy-ribose sugars are
used on the nucleotides in our alphabet. The name DNA stands for deoxy-ribose nucleic acid. A chain
structure closely related to DNA is what is called RNA, where the R refers to the fact that oxy-ribose
sugars or simply ribose sugars are used on the nucleotides in the alphabet used to build RNA. The
RNA alphabet is slightly different as the nucleotide Thymine,T, in the DNA alphabet is replaced by
the similar nucleotide Uracil, U. The chemical structure of uracil is shown in Figure 4.16(b) right next
to the formula for thymine. Note that the only difference is that carbon 5 C 0 holds a methyl group in
thymine and just a hydrogen in uracil. Despite these differences, uracil will still bond to adenine via
a complimentary bond.
It is rare for the long string of oxygenated ribose nucleotides to form a double helix, although
within that long chain of nucleotides there can indeed be local hairpin like structures and so forth.
Amino acids are coded using nucleotides with what is called the triplet code. This name came
about because any set of three nucleotides is used to construct one of the twenty amino acids through
57
a complicated series of steps. We will simply say that each triplet is mapped to an amino acid as a
shorthand for all of this detail. There are 20 amino acids and only 4 nucleotides. Hence, our alphabet
here is {A, C, T, G} The number of ways to take 3 things out of an alphabet of 4 things is 64. To see
this, think of a given triplet as a set of three empty slots; there are 4 ways to fill slot 1, 4 independent
ways to fill slot 2 (we know have 4 × 4 ways to fill the first two slots) and finally, 4 independent
ways to fill slot 3. This gives a total of 4 × 4 × 4 or 64 ways to fill the three slots independently.
Since there are only 20 amino acids, it is clear that more than one nucleotide triplet could be mapped
to a given amino acid! In a similar way, there are 64 different ways to form triplets from the RNA
alphabet {A, C, U, G}. We tend to identify these two sets of triplets and the associated mapping to
amino acids as it is just a matter of replacing the T in one set with an U to obtain the other set.
4.4 A Quick Look at How Proteins Are Made:
Organisms on earth have evolved to use this nucleotide triplet to amino acid mapping (it is not clear
why this is the mapping used over other possible choices!). Now proteins are strings of amino acids.
So each amino acid in this string can be thought of as the output of a mapping from the triplet code
we have been discussing. Hence, associated to each protein of length N is a long chain of nucleotides
of length 3N . Even though the series of steps by which the triplets are mapped into a protein is very
complicated, we can still get a reasonable grasp how proteins are made from the information stored in
the nucleotide chain by looking at the process with the right level of abstraction. Here is an overview
of the process:
• When a protein is built, certain biological machines are used to find the appropriate place in the
DNA double helix where a long string of nucleotides which contains the information needed
to build the protein is stored. This long chain of nucleotides which encodes the information to
build a protein is called a gene.
• Biological machinery unzips the double helix at this special point into two chains as shown in
Figure 4.17.
• A complimentary copy of a DNA single strand fragment is made using complimentary pair-
58
Figure 4.17: The Unzipped Double Helix
ing but this time adenine pairs to uracil to create a fragment of RNA. This fragment of RNA
serves to transfer information encoded in the DNA fragment to other places in the cell where
the actual protein can be assembled. Hence, this RNA fragment is given a special name –
Messenger RNA or mRNA for short. This transfer process is called transcription. For exam-
ple, the DNA fragment 5 ACCGT T ACCGT 3 would induce the complimentary DNA fragment
3
T GGCAAT GGCA5 , but in the cell, the complimentary RNA fragment 3 U GGCAAU GGCA5
is produced instead. Note again that the 5 pairs with a 3 and vice versa. There are many details
of course that we are leaving out. For example, there must be a special chunk of nucleotides
in the original DNA string that the specialized biological machines can locate as the place to
begin the unzipping process.
• The mRNA is transferred to a special protein manufacturing facility called the ribosome where
three nucleotides at a time from the mRNA string are mapped into their corresponding amino
acid. From what we said earlier, there are 64 different triplets that can be made from the alphabet
{A, C, U, G} and it is this mapping that is used to assemble the protein chain a little at a time.
• For each chain that is unzipped, a complimentary chain is attracted to it in the fashion shown by
59
Amino Acid DNA Triplet RNA Triplet

Alanine GCA, GCC, GCG, GCT GCA, GCC, GCG, GCU
Arginine AGA, AGG, CGA, CGC, CGG, CGT AGA, AGG, CGA, CGC, CGG, CGU
Asparagine AAC, AAT AAC, AAU
Aspartic Acid GAC, GAT GAC, GAU
Cysteine TAC, TAT UAC, UAU
Glutamic Acid GAA, GAG GAA, GAG
Glutamine CAA, CAG CAA, CAG
Glycine GGA, GGC, GGG, GGT GGA, GGC, GGG, GGU
Histidine CAC, CAT CAC, CAU
Isoleucine ATA, ATC, ATT AUA, AUC, AUU
Leucine CTA, CTC, CTG, CTT, TTA, TTG CUA, CUC, CUG, CUU, UUA, UUG
Lysine AAA, AAG AAA, AAG
Methionine (Start) ATG AUG
Phenylalanine TTC, TTT UUC, UUU
Proline CCA, CCC, CCG, CCT CCA, CCC, CCG, CCU
Serine AGC, AGT, TCA, TCC, TCG, TCT AGC, AGU, UCA, UCC, UCG, UCU
Threonine ACA, ACC, ACG, ACT ACA, ACC, ACG, ACU
Tryptophan TGG UGG
Tyrosine TAC, TAT UAC, UAU
Valine GTA, GTC, GTG, GTT GUA, GUC, GUG, GUU
Stop TAA, TAG, TGA UAA, UAG, UGA
Table 4.3: The Triplet Code
Table 4.2. This complimentary chain will however be built from the oxygenated deoxy-ribose
or simply ribose nucleotides. Hence, this complimentary chain is part of a complimentary RNA
helix.
• As the amino acids encoded by mRNA are built and exit from the ribosome into the fluid
inside the cell, the chain of amino acids or polypeptides begins to twist and curl into its three
dimensional shape based on all the forces acting on it.
We can write this whole process symbolically as DNA → mRNA → ribosome → Protein. This
is known as the Central Dogma of Molecular Biology.
Hence to decode a particular gene stored in DNA which has been translated to its complimentary
mRNA form all we need to know are which triplets are associated with which amino acids. These
triplets are called DNA Codons. The DNA alphabet form of this mapping is given in Table 4.3;
remember, the RNA form is the same, we just replace the thymine’s by uracil’s.
60
For example, the DNA sequence, T AC|T AT |GT G|CT T |ACC|T CG|AT T is translated into the
mRNA sequence AU G|AU A|CAC|GAA|U GG|AGC|U AA which corresponds to the amino acid
string
Start|Isoleucine|Histidine|Glutamic Acid|Tryptophan|Serine|Stop
Note that shifting the reading by one base to the right or left changes completely which triplets we
read for coding into amino acids. This is called a frame shift and it can certainly lead to a very
different decoded protein. Changing one base in a given triplet is a very local change and is a good
example of a mutation or a kind of damage produced by the environment or by aging or disease. Since
the triplet code is quite redundant, this may or may not result in a amino acid change. Even if it does,
it corresponds to altering one amino acid in a potentially long chain.
61
62
Chapter 5
Cell Membranes and Ion Movement:
We will now begin our study of a living cell. Our first abstract cell is a spherical ball which encloses
a fluid called cytoplasm. The surface of the ball is actually a membrane with an inner and outer part.
Outside the cell there is a solution called the extracellular fluid. Both the cytoplasm and extracellular
fluid contain many molecules, polypeptides and proteins disassociated into ions as well as sequestered
into storage units. In this chapter, we will be interested in what this biological membrane is and how
we can model the flow of ionized species through it. This modeling is difficult because some of the
ions we are interested in can diffuse or drift across the membrane and others must be allowed entry
through specialized holes in the membrane called gates or even escorted, i.e. transported or pumped,
through the membrane by specialized helper molecules. So we have a lot to talk about!
5.1 Membranes in Cells:
The functions carried out by membranes are essential to life. Membranes are highly selective per-
meability barriers instead of impervious containers because they contain specific pumps and gates
as we have mentioned. Membranes control flow of information between cells and their environment
because they contain specific receptors for external stimuli and they have mechanism by which they
can generate chemical or electrical signals. Membranes have several important common attributes:
• Membranes are sheet like structures a few molecules thick ( 60 - 100 Å).
63
• Membranes consist of specialized molecules called lipids together with proteins. The weight
ratio of proteins to lipids is about 4 : 1. They also contain specialized molecules called carbo-
hydrates (we haven’t yet discussed these) that are linked to the lipids and proteins.
• Membrane lipids are small molecules with a hydrophilic (i.e. attracted to water) and a hy-
drophobic (i.e. repelled by water) part. These lipids spontaneously assemble or form into
closed bimolecular sheets in aqueous medium. Essentially, it is energetically most favorable
for the hydrophilic parts to be on the outside near the water and the hydrophobic parts to be
inside away from the water. If you think about it a bit, it is not hard to see that forming a sphere
is a great way to get the water hating parts away from the water by placing them inside the
sphere and to get the water loving parts near the water by placing them on the outside of the
sphere. This lipid sheet is of course a barrier to the flow of various kinds of molecules.
• Specific proteins mediate distinctive functions of these membranes. Proteins serve as
1. pumps
2. gates
3. receptors
4. energy transducers
5. enzymes
• Membranes are non-covalent structures or assemblies. The constituent protein and lipid molecules
are held together by many non-covalent interactions which are cooperative.
• Membranes are asymmetric as the two faces of the membrane are different.
• Membranes are fluid structures that can be regarded as 2 − D solutions of oriented proteins and
lipids.
A typical membrane is built from what are called phospholipids which have the generic appear-
ance shown in Figure 5.1(a). Note the group shown in Figure 5.2(b) is polar and water soluble – i.e.
hydrophilic and the other side, Figure 5.2(a), is water phobic.
64
(a) A Typical Phospholipid (b) An Abstract Lipid
Figure 5.1: The Phospholipid Membrane Building Block And Abstract Membrane
(a) The Hydrophobic (b) The Hydrophilic Phospholipid End Group

Phospholipid End Group
Figure 5.2: Hydrophobic and Hydrophilic Phospholipids
Of course, this is way too much detail to draw; hence, we use the abstraction shown in Figure
5.1(b) using the term head for the hydrophilic part and tail for the hydrophobic part. Thus, these
lipids will spontaneously assemble so that the heads point out and the tails point in allowing us to
draw the self assembled membrane as in Figure 5.3(a).
We see the heads orient towards the water and the tails away from the water spontaneously into
this sheet structure. The assembly can also form a sphere rather than a sheet as shown in Figure 5.3(b).
A typical mammalian cell is 25 µm in radius where a µm is 10−6 meter. Since one Åis 10−10
meter or 10−4 µm, we see a cell’s radius is around 250,000 Å. Since the membrane is only 60 or so
Å is thickness, we can see the percentage of real estate of the cell concentrated in the membrane is
very small. So a molecule only has to go a small distance to get through the membrane but to move
65
(a) The Self Assembled Lipid Sheet Membrane (b) The Self Assembled Lipid
Structure Sphere Membrane Structure
Figure 5.3: Membrane Structures
through the interior of the cell (say to get to the nucleus) is a very long journey! Another way of
looking at this is that the cell has room in it for a lot of things!
5.2 The Physical Laws of Ion Movement:
We have relied on the wonderful books of Johnston and Wu (Johnston and Wu (8) 1995) and Weiss
(Weiss (14) 1996) in developing this discussion. They provide even more details and you should feel
free to look at these books. However, the amount of detail in them can be overwhelming, so we are
trying to offer a short version with just enough detail for our mathematical/ biological engineer and
computer scientist audience! An ion c can move across a membrane due to several forces.
5.2.1 Ficke’s law of Diffusion:
First, let’s talk about what concentration of a molecule means. For an molecule b, the concentration
molecules
of the ion is denoted by the symbol [b] and is measured in liter
. Now, we hardly ever measure
concentration in molecules per unit volume; instead we use the fact that there are 6.02 × 1023
M oles
molecules in a Mole and usually measure concentration in the units cm3
= M where for simplicity,
the symbol M denotes the concentration in Moles per cm3 . This special number is called Avogadro’s
66
Number and we will denote it by NA . In the discussions that follow, we will at first write all of
our concentrations in terms of molecules, but remember what we have said about Moles as we will
eventually switch to those units as they are more convenient.
The force that arises from the rate of change of the concentration of molecule b acts on the
molecules in the membrane to help move them across. The amount of molecules that moves across
per unit area due to this force is labeled the diffusion flux as flux is defined to a rate of transfer (
something
second
per unit area. Ficke’s Law of Diffusion is an empirical law which says the rate of change
of the concentration of molecule b is proportional to the diffusion flux and is written in mathematical
form as follows:
∂ [b]
Jdif f = −D (5.1)
∂x
where
molecules
• Jdif f is diffusion flux which has units of cm2 −second
.
cm2
• D is the diffusion coefficient which has units of second
.
molecules
• [b] is the concentration of molecule b which has units of cm3
.
The minus sign implies that flow is from high to low concentration; hence diffusion takes place down
the concentration gradient. Note that D is the proportionality constant in this law.
5.2.2 Ohm’s Law of Drift:
Ohm’s Law of Drift relates the electrical field due to an charged molecule, i.e. an ion, c across a
membrane to the drift of the ion across the membrane where drift is the amount of ions that moves
across the membrane per unit area. In mathematical form
Jdrif t = − ∂el E (5.2)
67
where it is important to define our variables and units very carefully. We have:
molecules
• Jdrif t is the drift of the ion which has units of cm2 −second
.
molecules
• ∂el is electrical conductivity which has units of volt−cm−second
.
We know from basic physics that an electrical field is the negative gradient of the potential so if V
is the potential across the membrane and x is the variable that measures our position on the membrane,
we have
∂V
E = −
∂x
Now the valence of ion c is the charge on the ion as an integer; i.e. the valence of Cl− is −1 and
the valence of Ca+2 is +2. We let the valence of the ion c be denoted by z. It is possible to derive the
following relation between concentration [c] and the electrical conductivity ∂el :
∂el = µ z [c]
where dimensional analysis shows us that the proportionality constant µ is called the mobility of ion
cm2
c and has units volt−second
. Hence, we can rewrite Ohm’s Law of Drift as
∂V
Jdrif t = −µz[c] (5.3)
∂x
We see that the drift of charged particles goes against the electrical gradient.
5.2.3 Einstein’s Relation:
There is a relation between the diffusion coefficient D and the mobility µ of an ion which is called
Einstein’s Relation. It says
68
κT
D = µ (5.4)
q
where
joule
• κ is Boltzmann’s constant which is 1.38 10−23 degree Kelvin .
• T is the temperature in degrees Kelvin.
• q is the charge of the ion c which has units of coulombs.
To see that the units work out, we have to recall some basic physics: we know that electrical work
κT volt−coulomb
is measured in volt − coulombs or joules. Hence, we see q
µ has units degree Kelvin degree kelvin
1 cm2
coulombs volt−second
which reduces to the units of D.
Further, we see that Einstein’s Law says that diffusion and drift processes are additive because
Ohm’s Law of Drift says Jdrif t is proportional to µ which by Einstein’s Law is proportional to D and
hence Jdif f .
5.2.4 Space Charge Neutrality:
When we look at a given volume element enclosed by a non permeable membrane, we also know
that the total charge due to positively charged ions, cations, and negatively charged ions, anions is
the same. If we have N cations ci with valences zi+ and M anions aj with valences zj− , we have the
charge due to an ion is its valence times the charge due to an electron e giving
N M
zi+ zj+ e [cj ]
X X
e [ci ] = (5.5)
i=1 j=1
Of course, in a living cell, the membrane is permeable, so equation 5.5 is not valid!
69
5.2.5 Ions, Volts and a Simple Cell:
The membrane capacitance of a typical cell is one micro fahrad per unit area. Typically, we use F
1coulomb
to denote the unit fahrads and the unit of area is cm2 . Also, recall that 1F = volt
. Thus, the
µF
typical capacitance is 1.0 cm 2 . Now our simple cell will be a sphere of radius 25 µM with the inside
and outside filled with a fluid. Let’s assume the ion c is in the extracellular fluid with concentration
[c] = 0.5M and is inside the cell with concentration [c] := .5M . The inside and outside of the cell are
separated by a biological membrane of the type we have discussed. We show our simple cell model
in Figure 5.4.
Figure 5.4: A Simple Cell
Right now in our picture, the number of ions on both sides of the membrane are the same. What
if one side had more or less ions than the other? These uncompensated ions would produce a voltage
difference across the membrane because charge is capacitance times voltage (q = cV ). Hence, if we
wanted to produce a one volt potential difference across the membrane, we can compute how many
uncompensated ions, δ[c] would be needed:
10−6 F coulombs
δ[c] = 2
× 1.0V = 10−6
cm cm2
Now the typical voltage difference across a biological membrane is on the order of 100 millivolts
70
(1 millivolt is 10−3 V and is abbreviated mV) or less. So to get a 100 mV difference, we need
10−6 coulombs
cm2
of uncompensated charge. Now the surface area, SA, and volume, V ol, of our simple
cell of radius r are
SA = 4πr2 = 7.854 × 10−5 cm2

4 3
V ol = πr = 6.545 × 10−8 cm3
3
Now the capacitance of the membrane per cm2 multiplied by the desired voltage difference of 100
mV will give the the uncompensated charge, n, per cm2 we need. Thus, we find
10−6 coulombs −1 −7 coulombs

n = × 10 V = 10
cm2 cm2
For convenience, let’s assume our ion c has a valence of −1. Now one electron has a charge of e of
n ions
1.6 × 10−19 coulombs, so the ratio e
tells us that 6.3 × 1011 cm2
are needed. Then the number of
uncompensated ions per cell to get this voltage difference is m = n SA giving
n
m = SA = 4.95 107 ions
e
This is a very tiny fraction of the total number of ions inside or outside the cell as for a .5M solution,
there are
ions
0.5 × NA Vol = 3.94 × 1013 ions
1000 liter
implying the percentage of uncompensated ions to give rise to a voltage difference of 100 mV is only
0.000126%.
71
5.3 The Nernst - Planck Equation:
Under physiological conditions, ion movement across the membrane is influenced by both electric
fields and concentration gradients. Let J denote the total flux, then we will assume that we can add
linearly the diffusion due to the molecule c and the drift due to the ion c giving
J = Jdrif t + Jdif f
Thus, applying Ohm’s Law 5.3 and Ficke’s Law 5.1, we have
∂V ∂[c]
J = −µ z [c] − D
∂x ∂x
Next, we use Einstein’s Relation 5.4 to replace the diffusion constant D to obtain what is called the
Nernst - Planck equation.
∂V κT ∂[c]
J = −µ z [c] Jdrif t − µ (5.6)
∂x q ∂x
!
∂V κT ∂[c]
= −µ z [c] Jdrif t +
∂x q ∂x
moles J
We can rewrite this result by moving to units that are cm2 −second
. To do this, note that NA
has the
proper units and using the Nernst-Planck equation 5.7 we obtain
!
J µ ∂V κT ∂[c]
= − z [c] + (5.7)
NA NA ∂x q ∂x
The relationship between charge and moles is given by Faraday’s Constant, F , which has the value
coulombs
F = 96, 480 mole
. Hence, the total charge in a mole of ions is the valence of the ion times
Faraday’s constant F , zF . Multiply equation 5.7 by zF on both sides to obtain
72
!
J µ zF ∂V κT ∂[c]
zF = − z [c] + (5.8)
NA NA ∂x q ∂x
This equation has the units of current per unit area because
J moles coulombs coulombs

zF = 2
=
NA cm − second mole cm2 − sec
amps
=
cm2
We can measure energy in two different units: joules (we use these in Boltzmann’s constant κ) or
calories. One calorie is the amount of energy needed to raise one gram of water at 25 degrees Centi-
grade one degree Centigrade. So it is certainly not obvious how to convert from joules to calories.
An argument that is based on low level principles from physics gives us the following conversion One
Calorie is 4.184 joules. From level physics, there is another fundamental physical constant called the
Gas Constant which is traditionally denoted by R. The constant can be expressed in terms of calories
or joules as follows:
1.98 calories
R =
degree Kelvin M ole
8.31 joules
=
degree Kelvin M ole
Hence, if we let q be the charge on one electron, e, we have for T is one degree Kelvin
joules
κ (T = 1) 1.38 10−23 degree Kelvin
= (1degree Kelvin)
q=e 1.6 10−19 coulombs
joules
= 8.614 10−5
coulomb
joules
R (T = 1) 8.31 degree Kelvin
=
F 96, 480coulomb
73
joules
= 8.614 10−5
coulomb
For later purposes, we will need to remember that
RT joules
= 8.614 10−5 (5.9)
F coulomb
κT RT
Thus, since q
is the same as F
, they are interchangeable in equation 5.8 giving
!
J µ ∂V ∂[c]
I = zF = − z 2 F [c] + z RT (5.10)
NA NA ∂x ∂x
amps
where the symbol I denotes this current density cm2
that we obtain with this equation. The current
I is the ion current that flows across the membrane per unit area due to the forces acting on the ion
c. Clearly, the next question to ask is what happens when this system is at equilibrium and the net
current is zero?
5.4 Equilibrium Conditions: The Nernst Equation:
The current form of the Nernst-Planck equation given in equation 5.10 describes ionic current flow
driven by electro-chemical potentials (concentration gradients and electric fields). We know that the
∂V ∂[c] ∂[c]
current I is opposite to ∂x
, with ∂x
if the valence z is negative and against ∂x
if the valence z is
positive. When the net current due to all of these contributions is zero, we have I = 0 and by the
Nernst-Planck Current Equation 5.10, we have
!
µ 2 ∂V ∂[c]
0 = − z F [c] + z RT
NA ∂x ∂x
implying
74
∂V ∂[c]
z 2 F [c] = −z RT
∂x ∂x
or since there is only one independent variable x
dV RT 1 d[c]
= −
dx zF [c] dx
This equation can be integrated as follows: between positions x1 and x2 , we find
Z x2 dV RT Z x2 d[c]
dx = − dx
x1 dx zF x1 [c]
Now assume that the membrane voltage and the concentration [c] are functions of the position x in
the membrane and hence can be written as V (x) and [c](x); we will then let V (x1 ) = V1 , V (x2 ) = V2 ,
[c](x1 ) = [c]1 and [c](x2 ) = [c]2 . Then, upon integrating, we find
Z V2 RT Z [c]2 d[c]
dV = −
V1 zF [c]1 [c]
RT [c]2
V2 − V1 = − ln
zF [c]1
It is traditional to define the membrane potential Vm of a cell to be the difference between the
inside (Vin and outside potential (Vout ; hence we say
Vm = Vin − Vout
For a given ion c, the equilibrium potential of the ion is denoted by Ec and is defined as the potential
across the membrane which gives a zero Nernst-Planck current. We will let the position x1 be the
75
place where the membrane starts and x2 , the place where the membrane ends. Here, the thickness of
the membrane is not really important. So the potential at x1 will be considered the inner potential Vin
and the potential at x2 will be considered the inner potential Vout . From our discussions above, we see
that the assumption that I is zero implies that the difference V1 − V2 is −Ec and so labeling [c]2 and
[c]1 as [c]out and [c]in respectively, we arrive at the following equation:
RT [c]out
Ec = ln (5.11)
zF [c]in
This important equation is called the Nernst equation and is an explicit expression for the equilibrium
potential of an ion species in terms of its concentrations inside and outside of the cell membrane.
5.4.1 An Example:
Let’s compute some equilibrium potentials. In Table 5.1, we see some typical inner and outer ion
concentrations and the corresponding equilibrium voltages. Unless otherwise noted, we will assume
a temperature of 70 degree Fahrenheit – about normal room temperature – which is 21.11 Celsius and
R
294.11 Kelvin as Kelvin is 273 plus Celsius.Since the factor F
is always a constant here, note
R 8.31 joules
= (5.12)
F 96, 480 coulomb − degrees Kelvin
V olts
= 8.61 10−5 (5.13)
degrees Kelvin
mV
= .0861 (5.14)
degrees Kelvin
Let’s look at some examples of this sort of calculation. While it is not hard to do this calculation,
we have found that all the different units are confusing to students coming from the mixed background
RT
we see. Now at a temperature of 294.11 Kelvin, F
becomes 25.32 mV. Hence, all of our equilibrium
voltage calculations take the form
76
1 [c]out
Ec = 25.32 ln mV
z [c]in
where all we have to do is to use the correct valence of our ion c. Also, remember that the symbol
ln means we should use a natural logarithm! Here are some explicit examples for this temperature:
1. For frog muscle, typical inner and outer concentrations for potassium are [K + ]out is 2.25 mM
(the unit mM means milli Moles) with [K + ]in at 124.0 mM. Then, since z is +1, we have
2.25
EK + = 25.32 ln mV
124.0
= 25.32 × (−4.0094) mV
= −101.5168 mV
2. For frog muscle, typical inner and outer concentrations for chlorine are [Cl− ]out is 77.5 mM
with [Cl− ]in at 1.5 mM. Then, since z is −1, we have
77.5
ECl− = −25.32 ln mV
1.5
= −25.32 × (3.944) mV
= −99.88 mV
3. For frog muscle, typical inner and outer concentrations for Calcium are [Ca+2 ]out is 2.1 mM
(the unit mM means milli Moles) with [Ca+2 ]in at 10−4 mM. Then, since z is +2, we have
2.1
EK + = 0.5 × 25.32 ln mV
10−4
= 12.66 × (9.9523) mV
= 126.00 mV
We summarize the results above as well as two other sets of calculations in Table 5.1. In the first
RT
two parts of the table we use a temperature of 294.11 Kelvin and the conversion F
is 25.32 mV. In
77
Frog Muscle (Conway 1957) [c]in [c]out Ec

K+ 124.0 2.25 -101.52
Na+ 10.4 109.0 59.30
Cl− 1.5 77.5 -99.88
Ca+2 10−4 2.1 126.00
Squid Axon (Hodgkin 1964)
K+ 400.0 20.0 -75.85
Na+ 50.0 440.0 55.06
Cl− 40.0 - 150.0 560.0 -66.82 - 33.35
Ca+2 10−4 10.0 145.75
Mammalian Cell
K+ 140.0 5.0 -88.94
Na+ 5.0 - 15.0 145.0 89.87 - 60.55
Cl− 4.0 110.0 -88.46
Ca+2 10−4 2.5 - 5.0 135.13 - 144.39
Table 5.1: Typical Inner and Outer Ion Concentrations
RT
the last part, the temperature is higher (310 Kelvin) and so F
becomes 26.69 mV. All concentrations
are given in mM.
5.5 One Ion Nernst Computations in MatLab:
Now let’s do some calculations using MatLab for various ions. First, we will write a MatLab function
to compute the Nernst voltage. Here is a simple MatLab function to do this
Listing 5.1: Computing The Nernst Voltage

f u n c t i o n v o l t a g e = N e r n s t ( v a l e n c e , T e m p e r a t u r e , InConc , OutConc )
%
% compute N e r n s t v o l t a g e f o r a g i v e n ion
%
5 R = 8.31;
T = Temperature +273.0;
F = 96480.0;
P r e f i x = ( R∗T ) / ( v a l e n c e ∗F ) ;
%
10 % output voltage in m i l l i v o l t s
%
v o l t a g e = 1 0 0 0 . 0 ∗ ( P r e f i x ∗ l o g ( OutConc / InConc ) ) ;
When we use this function, our MatLab session might look like this: first, we set our local paths:
78
%
% Our script files, <file_name>.m are in
% a directory local for us. We set that
% directory below so MatLab can find our files
%
>> path(path,’/local/petersj/BioInfo/Nernst’);
%
% The function which computes the Nernst voltage is
% in the file Nernst.m. We must name this file with
% the same name we use for the function. Yep. That is
% a bummer!
%
% So when we write the line below, MatLab will search for
% the file which defines the funtion Nernst.
%
Then, we compute a Nernst potential.
% Now this version has some diagnostic prints in it

% so you can see what is going on.
%
% We are computing the Nernst potential for
% a potassium ion. The valence is thus 1.
% We will use a temperature in Centigrade of
% 37 degrees C (quite hot!) and the inside
% concentration is 124 milliMoles with the
% outside concentration 2.5 milliMoles.
%
% Our function expects the argments to be
% entered as follows:
%
% Your variable name valence temperature(C) InsideConc OutsideConc
% | | | | |
% v v v v v
% E_K = Nernst(1, 37.0, 124, 2.5)
%
% so here is our line
>> E_K = Nernst(1,37.0,124,2.5)
This function call produces the following output (edited to remove extra blank lines)
valence =
1
Temperature =
37
79
OutConc =
2.5000
InConc =
124.5000
T =
310
F =
96480
Prefix =
0.0267
E_K =
-104.2400
>>
Now let’s do a simple plot. We are still in MatLab, so we divide the interval [15,37] into 200
uniformly spaced points and save these points into a vector called DegreesC.
>> DegreesC = linspace(15,37,200);
Using this vector, we call our Nernst voltage function to compute a corresponding vector of volt-
age values:
>> V_K = Nernst(1,DegreesC,124,2.5);
Now if you look at the top left part of your MatLab screen, you’ll see this window called ”Launch-
pad”. If the choice MatLab has a + sign next to it, you won’t see the extra options under it. So click
on the + and you’ll see a bunch of options including ”Workspace” unfold. Now double click on
”Workspace” and you’ll see all of our variables listed. You’ll see DegreesC and VK are vectors of size
1x200. Now let’s plot voltage vs temperature. The command below plots DegreesC on the horizontal
axis, VK on the vertical axis and uses green dashes to draw the curve (that is the ’g-’ command).
>> plot(DegreesC,V_K,’g-’);
Now we want to print this out to a file so we can use it in our web documents. Our stuff is unix
oriented, so you Windows people will have to sniff out some stuff on your own, but it will be similar.
You see the graph has popped up in a window called Figure No. 1 for us. Go to the file menu and pull
it down and select Export. If you click on the save as Save as type button, a bunch of output file types
80
will be shown. Pick the one you want. We want ”encapsulated postscript”, so we pick ”eps”. Then
we pick a name for our file; here we called potassium.eps.
Click the save button and you are done. If you want to see more stuff on plot, just type for help
like so:
>> help plot
As discussed above, we saved this plot as a file. In Figure ( 5.5), you can see what we have
generated:
Figure 5.5: The Potassium Voltage vs. Temperature
5.5.1 Exercises:
1. Use the MatLab functions we have written above to generate a plot of the Nernst potential
versus inside concentration for the Sodium ion at T = 20 degrees C. Assume the outside
concentration is always 440 milliMoles and let the inner concentration vary from 2 to 120 in
200 uniformly spaced steps.
2. Rewrite our Nernst and NernstMemVolt functions to accept temperature arguments in degrees
Fahrenheit.
3. Rewrite our NernstMemVolt function for just Sodium and Potassium ions.
81
82
Chapter 6
Electrical Signaling:
The electrical potential across the membrane is determined by how well molecules get through the
membrane ( its permeability ) and the concentration gradients for the ions of interest. To get a handle
on this let’s look at an imaginary cell which we will visualize as an array. The two vertical sides you
see on each side of the array represent the cell membrane. There is cell membrane on the top and
bottom of this array also, but we don’t show it. We will label the part outside the box as the Outside
and the part inside as Inside . If we wish to add a way for a specific type of ion to enter the cell, we
will label this entry port as Gates on the bottom of the array.We will assume our temperature is 70
degree Fahrenheit which is 21.11 Celsius and 294.11.
6.1 The Cell Prior to KCl Disassociation:
To get started, let’s assume no potential difference across the membrane and add 100 mM of KCl to
both the inside and outside of the cell as shown.
83
 
 
 
 

 Inside 

 
 
100mM 



 
 
Outside 
 100mM 

 
 
KCl 



 
 

 KCl 

 
 
The KCl promptly disassociates into an equal amount of K + and Cl− in both the inside and
outside of the cell as shown below:
 
 
 
 


 
 
100mMK + 



 
 
Outside 
 100mMK + 

 
 
100mMCl− 



 
 

 100mMCl− 

 
 
6.2 The Cell With K + Gates:
Now, we add to the cell channels that are selectively permeable to the ion K + . These gates allow K +
to flow back and forth across the membrane until there is a balance between the chemical diffusion
force and the electric force. We don’t expect a nonzero equilibrium potential because there is charge
and concentration balance already. Using Nernst’s Equation 5.11 we see since z is 1 that for our
RT
temperature, zF
is 25.32 mV and
84
RT [K + ]out
EK = ln
F [K − ]in
100
= 25.32 ln
100
= 0
 
 
 
 


 
 
 
 
100mMK + 




 100mMK + 

Outside 



 
 
100mMCl− 




 100mMCl− 

 
 
 
 
 
 
(K + Gates)
6.2.1 The Cell With Outer KCl Reduced:
Now reduce the outside KCl to a0 mM giving the following cell:
 
 
 
 


 
 
 
 
10mMK + 




 100mMK + 

Outside 



 
 
10mMCl− 




 100mMCl− 

 
 
 
 
 
 
(K + Gates)
85
This set up a concentration gradient with an implied chemical and electrical force. We see
10
EK = 25.32 ln
100
= −58.30
Hence, Vin − Vout is −58.30 mV and so the outside potential is 58.30 more than the inside; more
commonly, we say the inside is 58.30 mV more negative than the outside.
6.3 The Cell With NaCl Inside and Outside Changes:
Now add 100 mM NaCl to the outside and 10 mM to the inside of the cell. We then have
 
 
 
 


 
 
 
 
10mMK + 100mMN a+ 




 100mMK + 10mMN a+ 

Outside 



 
 
10mMCl− 100mMCl− 




 100mMCl− 10mMCl− 

 
 
 
 
 
 
(K + Gates)
Note there is charge balance inside and outside but since the membrane is permeable to K + ,
there is still a concentration gradient for K + . There is no concentration gradient for Cl− . Since
the membrane wall is not permeable to N a+ , the N a+ concentration gradient has no effect. The K +
concentration gradient is still the same as our previous example, the equilibrium voltage for potassium
remains the same.
86
6.4 The Cell with N a+ Gates:
Next replace the potassium gates with sodium gates as shown below. We can then use the Nernst
equation to calculate the equilibrium voltage for N a+ :
100
EN a = 25.32 ln
10
= 58.30
which is the exact opposite of the equilibrium voltage for potassium.
 
 
 
 


 
 
 
 
10mMK + 100mMN a+ 




 100mMK + 10mMN a+ 

Outside 



 
 




 100mMCl− 10mMCl− 

 
 
 
 
 
 
(N a+ Gates)
6.5 The Nernst Equation For Two Ions:
Let’s look at what happens if the cell has two types of gates. The cell now looks like this:
87
 
 
 
 


 
 
 
 
10mMK + 100mMN a+ 




 100mMK + 10mMN a+ 

Outside 



 
 




 100mMCl− 10mMCl− 

 
 
 
 
 
 
(K + Gates)(N a+ Gates)
There are now two currents: K + is leaving the cell because there is more K + inside than outside
and N a+ is going into the cell because there is more N a+ outside. What determines the resting
potential now?
Recall Ohm’s Law for a simple circuit: the current across a resistor is the voltage across the re-
V
sistor divided by the resistance; in familiar terms I = R
using time honored symbols for current,
voltage and resistance. It is easy to see how this idea fits here: there is resistance to the movement of
1
an ion through the membrane. Since I = R
R, we see that the ion current through the membrane is
1
proportional to the resistance to that flow. The term R
seems to be a nice measure of how well ions
1
flow or conduct through the membrane. We will call R
the conductance of the ion through the mem-
brane. Conductance is generally denoted by the symbol g. Clearly, the resistance and conductance
associated to a given ion are things that will require very complex modeling even if they are pretty
straightforward concepts. We will develop some very sophisticated models in future chapters, but for
now, for an ion c, we will use
Ic = gc (Vm − Ec )
where Ec is the equilibrium voltage for the ion c that comes from the Nernst Equation, Ic is the
ionic current for ion c and gc is the conductance. Finally, we denote the voltage across the membrane
88
to be Vm . Note the difference between the membrane voltage and the equilibrium ion voltage provides
the electromotive force or emf that drives the ion. In our cell, we have both potassium and sodium
ions, so we have
iK = gK (Vm − EK )
iN a = gN a (Vm − EN a )
At steady state, the current flows due to the two ions should sum to zero; hence
iK + iN a = 0
implying
0 = gK (Vm − EK ) + gN a (Vm − EN a )
which we can solve for the membrane voltage at equilibrium:
gK gN a
Vm = EK + EN a
gK + gN a gK + gN a
You will note that although we have already calculated EK and EN a here, we are not able to
compute Vm because we do not know the particular ionic conductances.
89
Figure 6.1: A Simple Membrane Model
6.6 The Nernst Equation For More Than Two Ions:
Consider Figure 6.1. We see we are thinking of a patch of membrane as a parallel circuit with one
branch for each of the three ions K + , N a+ and Cl− and a branch for the capacitance of the membrane.
We think of this patch of membrane as having a voltage difference of Vm across it. In general, there
will current that flows through each branch. We label these currents as IK , IN a , ICl and Ic where Ic
denotes the capacitative current. The conductances for each ion are labeled with resistance symbols
with a line through them to indicate that these conductances might be variable in a real model. For
right now, we will assume all of these conductances are constant.
Each of our ionic currents have the form
iion = gc (Vm − Ec )
where Vm , as mentioned, is the actual membrane voltage, c denotes our ion, gc is the conductance
associated with ion c and Ec is the Nernst equilibrium voltage). Hence for three ions, potassium (K + ),
sodium (N a+ ) and chlorine (Cl− ), we have
iK = gK (Vm − EK )
iN a = gN a (Vm − EN a )
iCl = gCl (Vm − ECl )
90
There is also a capacitative current. We know the voltage drop across the capacitor Cm is given
qm
by Vm
; hence, the charge across the capacitor is Cm Vm implying the capacitative current is
dVm
im = Cm
dt
At steady state, im is zero and the ionic currents must sum to zero giving
iK + iN a + iCl = 0
Hence,
0 = gK (Vm − EK ) + gN a (Vm − EN a ) + gCl (Vm − ECl )
leading to a Nernst Voltage equation for the equilibrium membrane voltage Vm of a membrane
permeable to several ions:
gK gN a gCl
Vm = EK + EN a + ECl
gK + gN a + gCl gK + gN a + gCl gK + gN a + gCl
We usually rewrite this in terms of conductance ratios: rN a is the gN a to gK ratio and rCl is the
gCl to gK ratio:
1 rN a rCl
Vm = EK + EN a + ECl
1 + rN a + rCl 1 + rN a + rCl 1 + rN a + rCl
Hence, if we are given the needed conductance ratios, we can compute the membrane voltage at
91
equilibrium for multiple ions. Some comments are in order:
• By convention, we set Vout to be 0 so that Vm = Vin − Vout is −58.3 mV in our first K+ gate
example.
• These equations are only approximately true, but still of great importance in guiding our under-
standing.
• Ion currents flowing through a channel try to move the membrane potential toward the equilib-
rium potential value for that ion.
• If several different ion channels are open, the summed currents drive the membrane potential to
a value determined by the relative conductances of the ions.
• Since an ion channel is open briefly, the membrane potentials can’t stabilize and so there will
always be transient ion currents. For example, if N a+ channels pop open briefly, there will be
transient N a+ currents.
Finally, let’s do a simple example: assume there are just sodium and potassium gates an the relative
conductances of N a+ and K + are 4 : 1. Then rN a is 4 and for the concentrations in our examples
above:
1 4
Vm = (−58.3)mV + (58.3)mV
5 5
= 34.98mV
6.7 Multiple Ion Nernst Computations in MatLab:
Now let’s do some calculations using MatLab for this situation. First, we will write a MatLab function
to compute the Nernst voltage across the membrane using our conductance model. Here is a simple
MatLab function to do this which uses our previous Nernst function. We will build a function which
assumes the membrane is permeable to using potassium, sodium and chlorine ions.
92
Listing 6.1: Computing The Membrane Voltage

%
%
5 R = 8.31;
F = 96480.0;
%
%
Let’s try this out for the following example: we assume we know
• The temperature is 20 degrees Celsius.
• The ratio gN a to gK is 0.03.
• The ratio of gC to gK is 0.1.
• The inside and outside concentrations for potassium are 400 and 20 milliMoles respectively.
• The inside and outside concentrations for sodium are 50 and 440 milliMoles respectively.
• The inside and outside concentrations for chlorine are 40 and 560 milliMoles respectively.
We then enter the function call into MatLab like this:
>> NernstMemVolt(20,0.03,0.1,400,20,50,440,40,560)
ans =
-71.3414
If there was a explosive change in the gN a to gK ratio (this happens in a typical axonal pulse which
we will discuss in later chapters), we see a large swing of the equilibrium membrane voltage from the
previous −71, 34 mV to 46.02. The code below resets this ratio to 15 from its previous value of 0.03:
>> NernstMemVolt(20,15.0,0.1,400,20,50,440,40,560)
ans =
46.0241
93
94
Chapter 7
Transport Mechanisms:
7.1 Transport Mechanisms:
There are five general mechanisms by which molecules are moved across biological membranes. All
of these methods operate simultaneously so we should know a little about all of them.
• Diffusion: here dissolved substances are transported because of concentration gradient. These
substances can go right through the membrane. Some examples are water, certain molecules
known as anesthetics and other large proteins which are soluble in the lipids which comprise
the membrane such as the hormones known as steroids.
• Transport Through Water Channels: water will flow from a region in which a dissolved sub-
stance is at high concentration in order to equalize a high - low concentration gradient. This
process is called osmosis and the force associated with it is called osmotic pressure. The bi-
ological membranes are thus semi-permeable to water and there are channels or pores in the
membrane which selectively allow the passage of water molecules. In Figure 7.1(b), we see an
abstract picture of the process of diffusion (part a) and the water channels (part b). The move-
ment of water from a high to low concentration environment of the ion c is shown in Figure
7.1(a)
• Transport Through Gated Channels: some ion species are able to move through a membrane
because there are special proteins embedded in the membrane which can be visualized as a
95
(a) Osmosis (b) Diffusion and Water Channel Transport
Figure 7.1: Transport Through Water Channels
cylinder whose throat can be open or blocked depending on some external signal. This external
signal can be the voltage across the membrane or a molecule called a trigger. If the external
signal is voltage, we call these channels voltage gates. When the gate is open, the ion is able to
physically move through the opening.
• Carrier Mediated Transport: in this case, the dissolved substance combines with a carrier
molecule on the one side of the membrane. The resulting complex that is formed moves through
the membrane. At the opposite end of the membrane, the solute is released from the complex.
A probable abstraction of this process is shown in Figure 7.2.
• Ion Pumps: ions can also be transported by a mechanism which is linked to the addition of an
OH group to the molecule adenine triphosphate. This process is called hydrolysis and this
common molecule is abbreviated ATP. The addition of the hydroxyl group to ATP liberates
energy. This energy is used to move ions against their concentration gradient.
In Figure 7.3, parts c through e, we see abstractions of the remaining types of transport embed-
ded in a membrane.
96
Figure 7.2: A Carrier Moves a Solute Through the Membrane
Figure 7.3: Molecular Transport Mechanisms
97
7.1.1 Ion Channels:
In Figure 7.4, we see a schematic of a typical voltage gate. Note that the inside of the gate shows a
structure which can be in an open or closed position. The outside of the gate has a variety of molecules
with sugar residues which physically extend into the extracellular fluid and carry negative charges on
their tips. At the outer edge of the gate, you see a narrowing of the channel opening which is called
the selectivity filter. As we have discussed, proteins can take on very complex three dimensional
shapes. Often, their actual physical shape can switch from one form to another due to some external
signal such as voltage. This is called a conformational change. In a voltage gate, the molecule which
can block the inner throat of the gate moves from its blocking position to its open position due to such
a conformational change. In fact, this molecule can also be in between open and closed as well.
The voltage gated channel is actually a protein macromolecule which is inserted into an opening
in the membrane called a pore. We note that
• this macromolecule is quite big (1800 - 4000 amino acids) with one or more polypeptide chains,
• 100’s of sugar residues hang off the extracellular face,
• when open, the channel is a water filled pore with a fairly large inner diameter which would
allow the passage of many things except that there is one narrow stretch of the channel called a
selectivity filter,
• the inside of the pore is lined with hydrophilic amino acids which therefore like being near the
water in the pore,
• the outside of the pore is lined with hydrophobic amino acids which therefore dislike water
contact. These lie next to the lipid bilayer
7.1.2 Passive Ion Transport:
Ion concentration gradients can be maintained by selective permeabilities of the membrane to various
ions. Most membranes are permeable to K + , maybe Cl− and much less permeable to N a+ and Ca+2 .
This type of passage of ions through the membrane requires no energy and so it is called the passive
98
Figure 7.4: Typical Voltage Channel
99
distribution of the ions. If there is no other way to transport ions, a cell membrane permeable to
several ion species will reach an equilibrium potential determined by the Nernst equation. Let c+n
denote a cation of valence n and a−m be an anion of valence −n. Then the Nernst equilibrium
potentials for these ions are given by
RT [c+n ]out
Ec = ln +n
nF [c ]in
RT [a−m ]out
Ea = ln −m
−mF [a ]in
At equilibrium, the ionic currents must sum to zero forcing these two potentials to be the same.
Hence, Vc is the same as Va and we find
RT [c+n ]out RT [a−m ]out

ln +n = ln −m
nF [c ]in −mF [a ]in
implying
m [c+n ]out [a−m ]in

ln +n = ln −m
n [c ]in [a ]out
Exponentiating these expressions, we find that the ion concentrations must satisfy the following
expression which is known as Donnan’s Law of Equilibrium.
1 1
[c+n ]out m [a−m ]in n
=
[c+n ]in [a−m ]out
K + and Cl− Donnan Equilibrium:
For example, for the ions K + and Cl− ,
100
 
 
 
 


 
 
[K + ]out 



 
 
Outside 
 [K + ]in 

 
 
[Cl− ]out 



 
 

 [Cl− ]in 

 
 
and we would have that at Donnan equilibrium, the inner and outer ion concentrations would
satisfy
[K + ]out [Cl− ]in

=
[K + ]in [Cl− ]out
or
[K + ]out [Cl− ]out = [K + ]in [Cl− ]in
K + , Cl− and A−m Donnan Equilibrium:
Now assume that there are other negative ions in the cell, say A−m . Then, [A−m ]out is zero and we
have
101
 
 
 
 


 
 
[K + ]out 



 
 
Outside 
 [K + ]in 

 
 
[Cl− ]out 



 
 

 [Cl− ]in [A−m ]in 

 
 
Then because there must be charge neutrality, [K + ]in = [Cl− ]in +[A−m ]in and [K + ]out = [Cl− ]out
Also, we must have the usual Donnan Equilibrium state (remember the ion A−m does not play a
role in this):
[K + ]out [Cl− ]out = [K + ]in [Cl− ]in
Thus,
[K + ]2in = [K + ]in ([Cl− ]in + [A−m ]in )
= [K + ]in [Cl− ]in + [K + ]in [A−m ]in
= [K + ]out [Cl− ]out + [K + ]in [A−m ]in
= [K + ]2out + [K + ]in [A−m ]in
> [K + ]2out
Hence, if we can only use passive transport mechanisms, we must have
[K + ]in > [K + ]out
102
Now in Table 5.1, we list some typical potassium inner and outer concentrations. Note that in all
of these examples, we indeed have the inner concentration exceeds the outer.
7.1.3 Active Transport Using Pumps:
There are many pumps within a cell that move substances in or out of a cell with or against a concen-
tration gradient.
• N a+ K + Pump: this is a transport mechanism driven by the energy derived from the hydrolysis
of ATP. Here 3 N a+ ions are pumped out and 2 K + ions are pumped in. So this pump gives
us sodium and potassium currents which raise [N a+ ]out and [K + ]in and decrease [N a+ ]in and
[K + ]out . From Table 5.1, we see that [N a+ ]out is typically bigger, so this pump is pushing N a+
out against its concentration gradient and so it costs energy.
• N a+ Ca+2 Pump: this pump drives out 3 N a+ ions inside the cell for every Ca+2 ion that is
moved out. Hence, this pump gives us sodium and calcium currents which raise [N a+ ]in and
[Ca+2 ]in and decrease [N a+ ]out and [Ca+2 ]in . Here, the N a+ movement is with its concentra-
tion gradient and so there is no energy cost.
• Ca+2 Pump:this pump is also driven by the hydrolysis of ATP but it needs the magnesium ion
M g +2 to work. We say M g +2 is a cofactor for this pump. Here, Ca+2 ] is pumped into a storage
facility inside the cell called the endoplasmic reticulum which therefore takes Ca+ 2 out of the
cytoplasm and so brings down [Ca+2 ]in .
• HCO3− Cl− Exchange: this is driven by the N a+ concentration gradient and pumps HCO3−
into the cell and CL− out of the cell.
• Cl − N a+ K + Co transport: This is driven by the influx of N a+ into the cell. For every one
N a+ and K + that are pumped into the cell via this mechanism, 2 Cl− are driven out.
7.1.4 A Simple Compartment Model:
Consider a system which has two compartments filled with ions and a membrane with K + and Cl−
gates between the two compartments as shown below:
103
 
 
 
 

 100mM A− 

 
 
 
 
 
 

 150mM K + 

 
 

 One 

 
 

 50mM Cl− 

 
 
 
 
 
 
 
 
 
 
(Cl− Gates)(K + Gates)
 
− +
 (Cl Gates)(K Gates) 
 
 
 
 
 
 
 
 
 
 

 0mM A− 

 
 

 T wo 

 
 

 150mM K + 

 
 
 
 
 
 

 150mM Cl− 

 
 
We will assume the system is held at the temperature of 70 degree Fahrenheit – about normal room
temperature – which is 21.11 Celsius and 294.11. This implies our Nernst conversion factor is 25.32
mV for K + and −25.32 for Cl− . Is this system is electrochemical equilibrium or ECE?
In each compartment, we do have space charge neutrality as in Compartment One, 150 mM of

K + balances 100 mM of A− and 50 mM of Cl− ; and in Compartment Two, 150 mM of K + balances
150 mM of Cl− . However, Cl− is not concentration balanced and so Cl− is not at ECE implying
that Cl− will diffuse into Compartment Two from Compartment One. This diffusion shifts ions in the
compartments to
104
 
 
 
 

 100mM A− 

 
 
 
 
 
 

 150mM K + 

 
 

 One 

 
 

 100mM Cl− 

 
 
 
 
 
 
 
 
 
 
 
− +
 
 
 
 
 
 
 
 
 
 

 0mM A− 

 
 

 T wo 

 
 

 150mM K + 

 
 
 
 
 
 

 100mM Cl− 

 
 
So to get concentration balance, 50 Cl− moves Compartment Two to Compartment One. Now
counting ion charges in each compartment, we see that we have lost space charge neutrality. We can
regain this by shifting 50 mM of K + from Compartment Two to Compartment One to give:
105
 
 
 
 

 100mM A− 

 
 
 
 
 
 

 200mM K + 

 
 

 One 

 
 

 100mM Cl− 

 
 
 
 
 
 
 
 
 
 
 
− +
 
 
 
 
 
 
 
 
 
 

 0mM A− 

 
 

 T wo 

 
 

 100mM K + 

 
 
 
 
 
 

 100mM Cl− 

 
 
Now we see that there is a concentration imbalance in K + ! The point here is that this kind of
analysis, while interesting, is so qualitative that is doesn’t give us the final answer quickly! To get to
the final punch line, we just need to find the Donnan Equilibrium point. This is where
[K + ]One [Cl− ]One = [K + ]T wo [Cl− ]T wo
From our discussion above, we know that the number of mM’s of K + and Cl− that move from
Compartment Two to Compartment One will always be the same in order to satisfy space charge
106
neutrality. Let x denote this amount. Then we must have
[K + ]One = 150 + x
[K + ]T wo = 150 − x
[Cl− ]T wo = 150 − x
[Cl− ]One = 50 + x
yielding after a little algebra:
(150 + x) (50 + x) = (150 − x) (150 − x)
7500 + 200x + x2 = 22, 500 − 300x2 + x2
500x = 15, 000
x = 30
So at ECE, we have
 
 
 
 

 100mM A− 

 
 
 
 
 
 

 180mM K + 

 
 

 One 

 
 

 80mM Cl− 

 
 
 
 
 
 
 
 
 
 
107
 
− +
 
 
 
 
 
 
 
 
 
 

 0mM A− 

 
 

 T wo 

 
 

 120mM K + 

 
 
 
 
 
 

 120mM Cl− 

 
 
What are the membrane voltages? Of course, they should match! Recall, in the derivation of the
Nernst equation, the voltage difference for ion c between side 2 and 1 was
Ec = V1 − V2
RT [c]2
= ln
zF [c]1
Here, Compartment One plays the role of side 1 and Compartment Two plays the role of side 2.
So for K + , we have
EK = VOne − VT wo
[K + ]T wo
= 25.32 ln
[K + ]One
120
= 25.32 ln
180
= −10.27mV
and for Cl− ,
108
ECl = VOne − VT wo
[Cl− ]T wo
= −25.32 ln
[Cl− ]One
120
= −25.32 ln
80
= −10.27mV
Are we at osmotic equilibrium? To see this, we need to add up how many ions are in each
compartment. In Compartment One, there are 360 ions and in Compartment Two there are 240
ions. Since there are more ions in Compartment One than Compartment Two, water will flow from
Compartment One to Compartment Two to try to dilute the ionic strength in Compartment One. We
are ignoring this effect here.
109
110
Chapter 8
Movement of Ions Across Biological

Membranes:
We now will work our way through another way to view the movement of ions across biological
membranes that was developed by Goldman in 1943 and Hodgkin and Katz in 1949. This is the
Goldman - Hodgkin - Katz or GHK model. Going though all of this will give you an increased
appreciation for both the kind of modeling we need to do: what to keep from the science, what the
throw away and what tools to use for the model itself . We start with defining carefully what we mean
by the word permeability. We have used this word before but always in a qualitative sense. Now we
will be quantitative.
8.1 Membrane Permeability:
Let’s consider a substance c moving across a biological membrane. We will assume that the relation-
ship between the number of moles of c moving across the membrane in unit time and unit area is
proportional to the change in concentration of c. This gives
Jmolar = −P ∆[c] (8.1)
111
where
moles
• Jmolar is the molar flux which is in the units cm2 −second
.
cm
• P is the membrane permeability of the ion c which has units of second
.
moles
• ∆[] is the change in the concentration of c measured in the units cm3
.
∂ [c] molecules
Ficke’s Law of diffusion gives Jdif f = −D ∂x
where Jdif f is measured in cm2 −second
. Hence,
moles
we can convert to cm2 −second
by dividing through by Avogadro’s number NA . This gives (remember,
partial differentiation becomes regular differentiation when there is just one variable)
Jdif f Dm d[c]
= −
NA NA dx
where we now explicitly label the diffusion constant as belonging to the membrane. These two
fluxes should be the same; hence
Dm d[c]
Jmolar = −P ∆[c] = − (8.2)
NA dx
We will want to use the above equation for the concentration of c that is in the membrane itself. So
we need to distinguish from the concentration of c inside and outside the cell and the concentration
in the membrane. We will let [c] denote the concentration inside and outside the cell and [cm ], the
concentration inside the membrane. Hence, we have
Dm d[cm ]
Jmolar = −P ∆[cm ] = − (8.3)
NA dx
Now a substance will probably dissolve differently in the cellular solution and in the biological
membrane, let’s model this quantitatively as follows: Let [c]in denote the concentration of c inside the
cell, and [c]out denote the concentration of c outside the cell. The membrane has two sides; the side
112
facing into the cell and the side facing to the outside of the cell. If we took a slice through the cell, we
would see a straight line along which we can measure our position in the cell by the variable x. We
have x is 0 when we are at the center of our spherical cell and x is x0 when we reach the inside wall
of the membrane (i.e. x0 is the radius of the cell for this slice). We will assume that the thickness of
the membrane is a uniform `. Hence, we are at position x0 + ` when we come to the outer boundary
of the membrane. Inside the membrane, we will let [cm ] denote the concentration of c. We know the
the membrane concentration will be some fraction of the cell concentration. So
[cm ](x0 + `) = βo [c]out
[cm ](x0 ) = βi [c]in
for some constants βi and βo . The ratio of the boundary concentrations of c and the membrane
concentrations is an important parameter. From the above discussions, we see these critical ratios are
given by:
[cm ]x0 +`
βo =
[c]out
[cm ]x0
βi =
[c]in
For this model, we will assume that these ratios are the same: i.e. βo = βi ; this common value
will be denoted by β. The parameter β is called the partition coefficient between the solution and
the membrane. We will also assume that the membrane concentration [cm ] varies linearly across the
membrane from [c]in at x0 to [c]out at x0 + `. This model is shown in Figure 8.1:
Thus, since we assume the concentration inside the membrane is linear, we have for some con-
stants a and b:
113
Figure 8.1: The Linear Membrane Concentration Model
114
[cm ](x) = a x + b
[cx0 ] = [cm ]in = β[c]in
[cx0 +` ] = [cm ]out = β[c]out
This implies that
[cm ]in = a x0 + b
[cm ]out = a (x0 + `) + b
= [cm ]in + a`
Thus, letting ∆C denote [c]out − [c]in , we have
[cm ]out − [cm ]in

a =
`
β
= ([c]out − [c]in )
`
β
= ∆C
`
We can also solve for the value of b:
b = [cm ]in − ax0

β
= [cm ]in − x0 ( ([c]out − [c]in ))
`
β β
= β(1 + )[c]in − [c]out
` `
Hence,
115
d[cm ] β
= ([c]out − [c]in )
dx `
Now recall that
Jmolar = −P ∆[cm ]
Dm d[cm ]
= −
NA dx
Dm β
= − ([c]out − [c]in )
NA `
Thus, we have way to express the permeability P in terms of low level fundamental constants:
Dm β
P =
NA `
Finally, letting µm be the mobility within the membrane, we note that Einstein’s relation tells us that
κT RT
Dm = q
µm = F
µm , so we conclude
βRT µm
P = (8.4)
`F NA
8.2 The Goldman-Hodgkin-Katz (GHK) Model:
The GHK model is based on several assumptions about how the substance c behaves in the membrane:
1. [cm ] varies linearly across the membrane as discussed in the previous subsection.
2. The electric field in the membrane is constant.
3. The Nernst-Planck equation holds inside the membrane.
116
We let V m (x) denote the voltage or potential and E m (x), the electrical field, in the membrane at
position x. By assumption (2), we know that E m (x) is a constant we will call E m in the membrane
for all x. Now we also know from standard physics that an electric field is the negative gradient of the
potential so
dV m
Em = −
dx
implying
dV m
−E m dx =
dx
Z x0 +` Z x0 +`
−E m dx = dV m
x0 x0
m
= Vout − Vinm
Hence, we have
−E m ` = Eout
m m
− Ein
The Nernst equation will hold across the membrane, so we have that the voltage due to c across the
membrane is Vcm with
Ec = Vcm
= Vinm − Vout
m
RT [c]
= ln out
zF [c]in
117
Further, by assumption (3), the Nernst-Planck equation holds across the membrane, so the ion current
in the membrane, [I m ] is given by
dV m d[cm ]
!
m µm 2 m
I = − z F [c ] + z RT
NA dx dx
Also, since,
dV m
= −E m
dx
m
Vout − Vinm
=
`
−Vcm
=
`
leading to
−Vcm d[cm ]
!
m µm
I = − z 2 F [cm ] + z RT
NA ` dx
m
µm 2 V µm d[cm ]
= z F [cm ] c − z RT
NA ` NA dx
This implies that
µm z 2 F [cm ] m µm d[cm ]
Im − Vc = − z RT (8.5)
NA ` NA dx
To make sense out of this complicated looking equation, we will make a change of variable: define
y m as follows:
µm z 2 F [cm ] m
ym = I m − Vc (8.6)
NA `
118
This implies that
dy m dI m µm z 2 F m [cm ]
= − Vc
dx dx NA ` dx
dI m
We know that at equilibrium, the current flow will be zero and so dx
= 0. Hence, at steady state,
we have
dy m µm z 2 F m [cm ]
= − Vc
dx NA ` dx
or
` dy m µm z [cm ]
− =
zF Vcm dx NA dx
[cm ]
This gives us an expression for the term dx
in Equation 8.5. Using our change of variable y m and
substituting for the concentration derivative, we find
µm z d[cm ]
!
m
y = −RT
NA dx
` dy m
!
= −RT −
zF Vcm dx
We have thus obtained the simpler differential equation
RT ` dy m
ym = (8.7)
zF Vcm dx
This equation can be integrated easily:
119
RT ` dy m
dx =
zF Vcm y m
Z x0 +` RT ` Z x0 +` dy m
dx =
x0 zF Vcm x0 ym
which gives
RT ` y m (x0 + `)
` = ln (8.8)
zF Vcm y m (x0 )
To simplify this further, we must go back to the definition of the change of variable y m . From Equation
8.6, we see
µm z 2 F [cm ](x0 + `) m
y m (x0 + `) = I m (x0 + `) − Vc
NA `
m m µm z 2 F [cm ](x0 ) m
y (x0 ) = I (x0 ) − Vc
NA `
At steady state the currents I m (x0 + `) and I m (x0 ) are the same value. Call this constant steady state
value I0m . Then we have
µm z 2 F [cm ](x0 + `) m
y m (x0 + `) = I0m − Vc
NA `
µm z 2 F [cm ](x0 ) m
y m (x0 ) = I0m − Vc
NA `
Finally, remember how we set up the concentration terms. We used the symbols [cm ]out to represent
[cm ](x0 + `) and [cm ]in to represent [cm ](x0 ). Thus, we have
120
µm z 2 F [cm ]out m
y m (x0 + `) = I0m − Vc
NA `
µm z 2 F [cm ]in m
y m (x0 ) = I0m − Vc
NA `
Now, to finish our derivation, let’s introduce an additional parameter ξ defined by
z F Vcm
ξ = (8.9)
RT
Recall that we defined the permeability by
Dm β
P =
NA `
Now from the definition of ξ and P, we find that Equation 8.8 gives
y m (x0 + `)
` = `ξ ln
y m (x0 )
Thus, after canceling ` from both sides, we obtain
y m (x0 + `)
ξ = ln
y m (x0 )
Now, plug in the expressions for the y m terms evaluated at x0 + ` and x0 to find
121
µm z 2 F [cm ]out
 
I0m − NA `
Vcm
ξ = ln  µm z 2 F [cm ](x0 )

I0m − NA `
V c
m
 
zµm
I0m − NA `
z F V c
m m
[c ]out
= ln  zµm

I0m − NA `
z F V c
m [cm ]
in
 
zµm
I0m − NA `
ξRT [cm ]out
= ln  zµm

I0m − NA `
ξRT [c m]
in
 
µm ξ RT z
I0m − NA `
[cm ]out
= ln  µm ξ RT z

I0m − NA `
[cm ]in
But we also know that by assumption
[cm ]out = β[c]out
[cm ]in = β[c]in
and so
µm ξ RT z m β RT µm
[c ]out = ξz [c]out
NA ` NA `
But we know from the definition of P that the fractional expression is just PF and so we have
µm ξ RT z m
[c ]out = zPF ξ [c]out
NA `
In a similar fashion, we can derive that
µm ξ RT z m
[c ]in = zPF ξ [c]in
NA `
122
Substituting these identities into expression for xi we derived earlier, we find
I m − zPF ξ [cm ]out

!
ξ = ln 0m
I0 − zPF ξ [cm ]in
Now exponentiate these expressions to get
ξ I0m − zPF ξ [cm ]out

e =
I0m − zPF ξ [cm ]in
(I0m − zPF ξ [cm ]in )eξ = I0m − zPF ξ [cm ]out
leading to
I0m (eξ − 1) = zPF ξ([cm ]in eξ − [cm ]out )
We can solve the above equation for the steady state current term I0m . This gives
[cm ]in eξ − [cm ]out

!
I0m = zPF ξ
eξ − 1
When we replace xi by its definition and reorganize the resulting expression, we obtain the GHK
current equation for the ion c.
zF Vcm
 
z 2 PF 2 Vcm  [cm ]in − [cm ]out e− RT
I0m = zF Vcm
 (8.10)
RT 1 − e− RT
123
8.3 The GHK Voltage Equation:
Consider a cell that is permeable to K + , Cl− and N a+ ions with no active pumping. Let’s calculate
the resting potential of the cell. For each ion, we can apply our GHK theory to obtain an ionic current,
IK , IN a and ICl . At equilibrium, the current through the membrane should be zero and so all of the
ionic currents should sum to zero. Thus
IK + IN a + ICl = 0
Further, the associated Nernst potentials for the ions should all match because otherwise there
would be current flow:
V0m = VKm+ = VN a+ = VCl

m
−
where we denote this common potential by V0m . From the GHK current equation, we have (note the
valences for potassium and sodium are +1 and for chlorine is −1)
F V0m
 
2 −
PK F V0m + +
 [K ]in − [K ]out e RT
IK =

FV m
RT
 
0
1 − e− RT
F V0m
 
2 −
PN a F V0m +
 [N a ]in − [N a ]out e
+ RT
IN a =

FV m
RT
 
− 0
1 − e RT
−F V0m
 
PCl F 2 V0m  [Cl− ]in − [Cl− ]out e− RT
ICl =

−F V m
RT
 
0
1 − e− RT
F V0m
For convenience, let ξ0 denote the common term RT
. Then we have
[K + ]in − [K + ]out e−ξ0

!
IK = PK F ξ0
1 − e−ξ0
124
[N a+ ]in − [N a+ ]out e−ξ0

!
IN a = PN a F ξ0
1 − e−ξ0
[Cl− ]in − [Cl− ]out eξ0
!
ICl = PCl F ξ0
1 − eξ0
Now sum these ionic currents to obtain
[K + ]in − [K + ]out e−ξ0 [N a+ ]in − [N a+ ]out e−ξ0

! !
0 = PK F ξ0 + PN a F ξ0
1 − e−ξ0 1 − e−ξ0
[Cl− ]in e−ξ0 − [Cl− ]out
!
− PCl F ξ0
1 − e−ξ0
or
F ξ0 + + −

0 = PK [K ]in + PN a [N a ] in + PCl [Cl ]out − PK [K + ]out + PN a [N a+ ]out + PCl [Cl]i
1 − e−ξ0
Rewriting, we obtain

eξ0 PK [K + ]in + PN a [N a+ ]in + PCl [Cl− ]out = PK [K + ]out + PN a [N a+ ]out + PCl [Cl]in
PK [K + ]out + PN a [N a+ ]out + PCl [Cl]in
eξ0 =
PK [K + ]in + PN a [N a+ ]in + PCl [Cl− ]out
Finally, taking logarithms, we obtain the GHK Voltage equation for these ions:

!
RT
V0m = ln (8.11)
F PK [K + ]in + PN a [N a+ ]in + PCl [Cl− ]out
Now to actually compute the GHK voltage, we will need the values of the three permeabilities. It is
common to rewrite this equation in terms of permeability ratios. We choose one of the permeabilities
as the reference, say PN a , and compute the ratios
125
PK
rK =
PN a
PCl
rCl =
PN a
We can then rewrite the GHK voltage equation as
[N a+ ]out + rK [K + ]out + rCl [Cl]in

!
RT
V0m = ln (8.12)
F [N a+ ]in + rK [K + ]in + rCl [Cl− ]out
8.3.1 Examples:
Now let’s use the GHK voltage equation for a few sample calculations.
A First Example:
Consider a squid giant axon. Typically, the axon at rest has the following permeability ratios:
PK : PN a : PCl = 1.0 : 0.03 : 0.1
where we interpret this string of ratios as
PK 1.0
= = 33.33
PN a 0.03
PN a 0.03
= = 10.0
PCl 0.1
Thus, we have
PK
rK = = 33.33
PN a
126
PCl
rCl = : 0.3333
PN a
Now look at the part of Table 5.1 which shows the ion concentrations for the squid axon. As we
RT
discussed in Chapter 5, we will use a temperature of 294.11 Kelvin and the conversion F
is 25.32
mV. Also, recall that all concentrations are given in mM. Thus, the GHK voltage equation for the
squid axon gives
[N a+ ]out + rK [K + ]out + rCl [Cl]in

!
RT
V0m = ln
F [N a+ ]in + rK [K + ]in + rCl [Cl− ]out
440.0 + 33.33 × 20.0 + 0.3333 × 40.0

= 25.32(mV ) ln
50.0 + 33.33 × 400.0 + 0.3333 × 560.0
= 25.32(mV ) ln 1119.93213568.648
= −63.16 mV
A Second Example:
Now assume there is a drastic change in these permeability ratios: we now have:
PK : PN a : PCl = 1.0 : 15.0 : 0.1
where we interpret this string of ratios as
PK 1.0
= = 33.33
PN a 15.0
PN a 15.0
= = 10.0
PCl 0.1
Thus, we have
127
PK
rK = = 0.0667
PN a
PCl
rCl = : 0.00667
PN a
The GHK voltage equation now gives
440.0 + 0.0667 × 20.0 + 0.00667 × 40.0

V0m = 25.32(mV ) ln
50.0 + 0.0667 × 400.0 + 0.00667 × 560.0
= 25.32(mV ) ln 441.6080.4152
= 43.12 mV
We see that this large change in the permeability ratio between potassium and sodium triggers a
huge change in the equilibrium voltage across the membrane. It is actually far easier to see this effect
when we use permeabilities than when we use conductances. So as usual, insight is often improved by
looking at a situation using different parameters! Later, we will begin to understand how this explosive
switch from a negative membrane voltage to a positive membrane voltage is achieved. That’s for a
later chapter!
8.4 The Effects of an Electrogenic Pump:
We haven’t talked much about how the pumps work in our model yet, so just to give the flavor of such
calculations, let’s look at a hypothetical pump for an ion c. Let Ic denote the passive current for the
ion which means no energy is required for the ion flow (see Chapter 7 for further discussion). The ion
current due to a pump requires energy and we will let Icp denote the ion current due to the pump. At
steady state, we would have
IN a+ + INp a+ = 0
128
p
IK + + IK + = 0
Let the parameter r be the number of N a+ ions pumped out for each K + ion pumped in. This
then implies that
p p
rIK + + IN a+ = 0
From the GHK current equation, we know
[K + ]in − [K + ]out e−ξ0

!
IK + = PK F ξ0
1 − e−ξ0
[N a+ ]in − [N a+ ]out e−ξ0
!
IN a+ = PN a F ξ0
1 − e−ξ0
and thus from our steady state assumptions, we find
IN a+ = −INp a+
p
IK + = −IK +
and so
rIK + + IN a+ = 0 (8.13)
Substituting the GHK current expressions into Equation 8.13, we have
F ξ0
+ + −ξ0

+ + −ξ0

rPK [K ] in − [K ] out e + PNa [N a ] in − [N a ]out e = 0
1 − e−ξ0
129
giving

rPK [K + ]in − [K + ]out e−ξ0 − PN a [N a+ ]in − [N a+ ]out e−ξ0 = 0

rPK [K + ]in + PN a [N a+ ]in − rPK [K + ]out + PN a [N a+ ]out e−ξ0 = 0
We can manipulate this equation a bit to get

rPK [K + ]in + PN a [N a+ ]in = rPK [K + ]out + PN a [N a+ ]out e−ξ0
or
rPK [K + ]out + PN a [N a+ ]out

eξ0 =
rPK [K + ]in + PN a [N a+ ]in
Since we know that
F V0m
ξ0 =
RT
we can solve for V0m and obtain
rPK [K + ]out + PN a [N a+ ]out

!
RT
V0m =
F rPK [K + ]in + PN a [N a+ ]in
The N a+ − K + pump moves out 3N a+ ions for every 2K+ ions that go in. Hence the pumping
ratio is r is 1.5. Thus for our usual squid axon using only potassium and sodium ions and neglecting
chlorine, we find for a permeability ratio of
130
PK : PN a = 1.0 : 0.03
that
1.5 33.33 20.0 + 440.0

V0m = 25.32(mV ) ln
1.5 33.33 400.0 + 50.0
1439.90
= 25.32(mV ) ln
200480.0
= −66.68 mV
Without a pump, r will be 1 and the calculation becomes
33.33 20.0 + 440.0

V0m = 25.32(mV ) ln
33.33 400.0 + 50.0
1106.60
= 25.32(mV ) ln
13382.0
= −63.11 mV
Our sample calculation thus shows that the pump contributes −66.68 − −63.11 mV or −3.57 mV to
3.57
the rest voltage. This is only 66.68
or 5.35 percent!
8.5 Excitable Cells:
There are specialized cells in most living creatures called neurons which are adapted for generat-
ing signals which are used for the transmission of sensory data, control of movement and cognition
through mechanisms we don’t fully understand. However, a neuron is an example of what is called an
excitable cell which is a whose membrane is studded with many voltage gated sodium and potassium
channels. In terms of ionic permeabilities, the GHK voltage equation for the usual sodium, potassium
and chlorine ions gives
131

!
V0m = 25.32 (mV ) ln
PK [K + ]in + PN a [N a+ ]in + PCl [Cl− ]out
which is about −60 mV at rest but which we have already seen can rapidly increase to +40 mV upon
a large shift in the sodium and potassium permeability ratio. Recalling our discussion in Chapter 6,
we can also write the rest voltage in terms of conductances as
gK gN a gCl
V0m = EK + EN a + ECl
gK + gN a + gCl gK + gN a + gCl gK + gN a + gCl
Either the conductance or the permeability model allows us to understand this sudden increase in
voltage across the membrane in terms of either sodium to potassium permeability or conductance
ratio shifts.
We will study all of this in a lot of detail later, but for right now, let’s just say that under certain
circumstances, the rest potential across the membrane can be stimulated just right to cause a rapid
rise in the equilibrium potential of the cell, followed by a sudden drop below the equilibrium voltage
and then ended by a slow increase back up to the rest potential. The shape of this wave form is very
characteristic and is shown in Figure 8.2. This type of wave form is called an action potential and is
a fundamental characteristic of excitable cells.
In the figure, we draw the volt-

age across the membrane and simul-
taneously we draw the conductance
curves for the sodium and potas-
sium ions. Recall that conductance
is reciprocal resistance, so a spike in
sodium conductance, for example, is
proportional to a spike in sodium ion
current. So in the figure we see that
132
sodium current spikes first and potas-

sium second. Now that we have dis-
cussed so many aspects of cellular
membranes, we are at a point where
we can develop a qualitative under-
standing of how this behavior is gen-
erated. We can’t really understand
the dynamic nature of this pulse yet (that is it’s time and spatial dependence) but we can explain in
a descriptive fashion how the potassium and sodium gates physical characteristics cause the behavior
we see in Figure 8.2.
The changes in the sodium and potassium conductances that we see in the action potential can
be explained by molecular properties of the sodium and potassium channels. As in the example
we worked through for the resting potential for the squid nerve cells, for this explanation, we will
assume the chlorine permeability or equivalently the chlorine conductance does not change. So all
the qualitative features of the action potential will be explained solely in terms of relative sodium to
potassium conductance ratios. We have already seen that if we allow a huge increase in the sodium
to potassium conductance ratio, we generate a massive depolarization of the membrane. So now, we
will try to explain how this happens. We have talked about basic voltage operated gates before in
Chapter 7, but now let’s specialize to a typical sodium channel as shown in Figure 8.3. The drawing
of a potassium channel will be virtually identical.
When you look at the drawing of the sodium channel, you’ll see it is drawn in three parts. Our
idealized channel has a hinged cap which can cover the part of the gate that opens into the cell. We
call this the inactivation gate . It also has a smaller flap inside the gate which can close off the throat
of the channel. This is called the activation gate . As you see in the drawing, these two pieces can be
in one of three positions: resting (activation gate is closed and the inactivation gate is open); open
(activation gate is open and the inactivation gate is open); and closed (activation gate is closed or
closed and the inactivation gate is closed). Since this is a voltage activated gate, the transition from
resting to open depends on the voltage across the cell membrane. We typically use the following
terminology:
133
Figure 8.3: A Typical Sodium Channel
134
• When the voltage across the membrane is above the resting membrane voltage, we say the cell
is depolarized .
• When the voltage across the membrane is below the resting membrane voltage, we say the cell
is hyperpolarized .
These gates transition from resting to open when the membrane depolarizes. In detail, the proba-
bility that the gate opens increases upon membrane depolarization. However, the probability that the
gate transitions from open to closed is NOT voltage dependent. Hence, no matter what the membrane
voltage, once a gate opens, there is a fixed probability it will close again.
Hence, an action potential can be described as follows: when the cell membrane is sufficiently
depolarized, there is an explosive increase in the opening of the sodium gates which causes a huge
influx on sodium ions which produces a short lived rapid increase in the voltage across the membrane
followed by a rapid return to the rest voltage with a typical overshoot phase which temporarily keeps
the cell membrane hyperpolarized. We can explain much of this qualitatively as follows:
The voltage gated channels move randomly back and forth between their open and closed states.
At rest potential, the probability that a channel will move to the open position is small and hence,
most channels are in the closed position. When the membrane is depolarized from some mechanism,
the probability that a channel will transition to the open position increases. If the depolarization of
the membrane lasts long enough or is large enough, then there is an explosive increase in the cell
membrane potential fueled by
Explosive Depolarization of the Membrane • The depolarization causes a few N a+ channels

to open. This opening allows N a+ to move into the cell through the channel which in-
crease the inside N a+ concentration. Now our previous attempts to explain the voltage
across the membrane were all based on equilibrium or steady state arguments; here, we
want to think about what happens in that brief moment when the N a+ ions flood into the
cell. This is not a steady state analysis. Here, the best way to think of it is that the number
of plus ions in the cell has gone up. So since the electrical field is based on minus to
plus gradients, we would anticipate that the electrical field temporarily increases. We also
know from basic physics that
135
dV
E = −
dx
implying since the membrane starts at x0 and ends at x0 + ` that
E` = −(V (x0 + `) − V (x0 )
We have always labeled the voltage at the inside, V (x0 ) as Vin and the other as Vout .
Hence, since
V0m = Vin − Vout
we see that
E` = V0m
We see if we let N a+ ions in, the electric field goes up and so does the potential across
the membrane. Hence, the initial depolarizing event further depolarizes the membrane .
• This additional depolarization of the membrane increases the probability that the sodium
gates open. Hence, more sodium gates transition from resting to closed and more N a+
ions move into the cell causing further depolarization as outlined above.
• We see depolarization induces further depolarization which is known as positive feedback

.
• Roughly speaking, the membrane voltage begins to drive towards EN a as determined by

the Nernst voltage equation. For biological cells, this is in the range of 70 mV. Qualita-
136
tively, this is the portion of the voltage curve that is rising from rest towards the maximum
in Figure 8.2.
Sodium Inactivation • The probability that a sodium gate will move from open to closed is in-
dependent of the membrane voltage. Hence, as soon as sodium gates begin to open, there
is a fixed probability they will then begin to move towards closed. Hence, even as the
membrane begins its rapid depolarization phase, the sodium gates whose opening pro-
vided the trigger begin to close. This is most properly described in terms of competing
rates in which one rate is highly voltage dependent, but we can easily see that essentially
, the membrane continues to depolarize until the rate of gate closing exceeds the rate of
opening and the net flow of sodium ions is out of the cell rather than into the cell. At this
point, the membrane voltage begins to fall.
• The sodium gate therefore does not remain open for long. It’s action provides a brief spike
in sodium conductance as shown in Figure 8.4
Potassium Channel Effects • The potassium gate is also a voltage dependent channel whose
graphical abstraction is similar to that shown in Figure 8.3.
• These channels respond much slower to the membrane depolarization induced by the
sodium channel activations. As the K + channels open, K + inside the cell flows outward
and thereby begins to restore the imbalance caused by increased N a+ in the cytoplasm.
The explanation for this uses the same electrical field and potential connection we invoked
earlier to show why the membrane depolarizes. This outward flow, however, moves the
membrane voltage the other way and counteracts the depolarization and tries to move the
membrane voltage back to rest potential.
• The K+ channels stay open a long time compared to the N a+ channels. Since the sodium
channels essentially pop open and then shut again quickly, this long open time of the
potassium channel means the potassium conductance, gK falls very slowly to zero.
• As the potassium outward current overpowers the diminishing sodium inward current, the
potential accelerates its drop towards rest which can be interpreted as a drive towards the
137
Nernst potential EK which for biological cells is around −80 mV.
Chlorine Ion Movement The rest potential is somewhere in between the sodium and potassium
Nernst potentials and the drive to reach it is also fueled by several other effects. There is also
a chlorine current which is caused by the movement of chlorine through the membrane without
gating. The movement of negative ions into the cell is qualitatively the same as the movement
of positive potassium ions out of the cell – the membrane voltage goes down. Thus, chlorine
current in the cell is always acting to bring the cell back to rest. We see the cell would return to
its rest voltage even without the potassium channels, but the potassium channels accelerate the
movement. One good way to think about it is this: the potassium channels shorten the length
of time the membrane stays depolarizes by reducing the maximum height and the width of the
pulse we see in Figure 8.2.
The N a+ - K + Pump The active sodium - potassium pump moves 3 sodium ions out of the cell for
each 2 potassium ions that are moved in. This means that the cell’s interior plus charge goes
down by one. This means the membrane voltage goes down. Hence, the pump acts to bring the
membrane potential back to rest also.
The Hyperpolarization Phase In Figure 8.2, you can see that after the downward voltage pulse
crosses the rest potential line, the voltage continues to fall before it bottoms out and slowly
rises in an asymptotic fashion back up to the rest potential. This is called the hyperpolarization
phase and the length of time a cell spends in this phase and the shape of the this phase of the
curve are important to how this potential change from this cell can be used by other cells for
communication. As the potassium channels begin to close, the K + outward current drops and
the voltage goes up towards rest.
The Refractory Period During the hyperpolarization phase, many sodium channels are inactivated.
The probability a channel will reopen simultaneously is small and most sodium gates are closed.
So for a short time, even if there is an initial depolarizing impulse event, only a small number of
sodium channels are in a position to move to open. However, if the magnitude of the depolar-
ization event is increased, more channels will open in response to it. So it is possible that with
138
a large enough event, a new positive feedback loop of depolarization could begin and generate
a new action potential. However, without such an event, the membrane is hyperpolarized, the
probability of opening is a function of membrane voltage and so is very low, and hence most
gates remain closed. The membrane is continuing to move towards rest though and the closer
this potential is to the rest value, the higher the probability of opening for the sodium gates.
Typically, this period where the cell has a hard time initiating a new action potential is on the
order of 1 − 2 mS. This period is called the refractory period of the cell.
With all this said, let’s go back to the initial depolarizing event. If this event is a small pulse of
N a+ current that is injected into a resting cell, there will be a small depolarization which does not
activate the sodium channels and so the ECE force acting on the K + and Cl− ions increase. K +
goes out of the cell and Cl− comes in. This balances the inward N a+ ion jet and the cell membrane
voltage returns to rest. If the initial depolarization is larger, some N a+ channels open but if the K +
and Cl− net current due to the resulting ECE forces is larger than the inward N a+ current due to the
jet and the sodium channels that are open, the membrane potential still goes back to rest. However,
if the depolarization is sufficiently large, the ECE derived currents can not balance the inward N a+
current due to the open sodium gates and the explosive depolarization begins.
Figure 8.4: Sodium Conduc-

tance Spiking
139
140
Chapter 9
Lumped and Distributed Cell Models
We can now begin to model a simple biological cell. We can think of a cell as having an input line
(this models the dendritic tree), a cell body (this models the soma) and an output line (this models
the axon). We could model all these elements with cables – thin ones for the dendrite and axon and
a fat one for the soma. To make our model useful, we need to understand how current injected into
the dendritic cable propagates a change in the membrane voltage to the soma and then out across the
axon. Our simple model is very abstract and looks like that of Figure 9.1.
Note that the dendrite in Figure 9.1 is of length L and its position variable is w and the soma also
has length L and its position variable is w. Note that each of these cables has two endcaps – the right
and left caps on the individual cylinders – and we eventually will have to understand the boundary
conditions we need to impose at these endcaps when current is injected into one of these cylinders.
We could also model the soma as a spherical cell, but for the moment let’s think of everything as the
cylinders you see here. So to make progress on the full model, we first need to understand a general
model of a cable.
Figure 9.1: A Simple Cell Model
141
(a) The Cable Cylinder Model (b) 2D Cross-section
Figure 9.2: Cable Cylinders
9.1 Modeling Radial Current:
Now a fiber or cable can be modeled by some sort of cylinder framework. In Figure 9.2(a), we show
the cylinder model. In our cylinder, we will first look at currents that run out of the cylinder walls
and ignore currents that run parallel or longitudinally down the cylinder axis. We label the interesting
variables as follows:
• The inner cylinder has radius a.
• L is the length of the wire.
• V is the voltage across the wall or membrane.
• Ir is the radial current flow through the cylinder. This means the current is flowing through the
walls. This is measured in amps.
amps
• Jr is the radial current flow density which has units of amps per unit area –for example, cm2
.
amps
• Kr is the radial current per unit length – typical units would be cm
.
The 2D cross-section shown in Figure 9.2(b), further illustrates that the radial current Jr moves
out of the cylinder.
Clearly, since the total surface area of our cylinder is 2πaL, we have the following conversions
between the various current variables.
142
(a) The Cable Cylinder Model (b) Part of the Cable Bilipid Membrane Structure
Cross Section
Figure 9.3: Cable Details
Ir = 2πaL Jr
Ir
Kr = = 2πa Jr
L
Now, imagine our right circular cylinder as being hollow with a very thin skin filled with some
conducting solution, as shown in Figure 9.3(a). Further, imagine the wall is actually a bilipid layer
membrane as shown in Figure 9.3(b).
We know have a simple model of a biological cable we can use for our models. This is called
the annular model of a cable. In other words, if we take a piece of dendritic or axonal fiber, we can
model it as two long concentric cylinders. The outer cylinder is filled with a fluid which is usually
considered to be the extracellular fluid outside the nerve fiber itself. The outer cylinder walls are
idealized to be extremely thin and indeed we don’t usually think about them much. In fact, the outer
cylinder is actually just a way for us to handle the fact that the dendrite or axon lives in an extracellular
fluid bath. The inner cylinder has a thin membrane wall wrapped around an inner core of fluid. This
inner fluid is the intracellular fluid and the membrane wall around it is the usual membrane we have
discussed already. The real difference here is that we are now looking at a specific geometry for our
143
membrane structure.
9.2 Modeling Resistance:
We also will think of these cables as much as possible in terms of simple circuits. Hence, our finite
piece of cable should have some sort of resistance associated with it. We assume from standard
physics that the current density per unit surface area, Jr , is proportional to the electrical field density
per length E. The proportionality constant is called conductivity and is denoted by σe . The resulting
equation is thus
Jr = σe E
Another traditional parameter is called the resistivity which is reciprocal conductivity and is labeled
ρ.
1
ρ =
σe
The units here are
V olts
• E is measured in cm
.
1
• σe is measured in ohm−cm
.
• ρ is measured in ohm − cm.
V olts amps
This gives us the units of ohm−cm2
or cm2
for the current density Jr which is what we expect them to
be! The parameters ρ and σe measure properties that tell us what to do for one cm of our cable but do
not require us to know the radius. Hence, these parameters are material properties .
144
Figure 9.4: Longitudinal Cable Currents
9.3 Longitudinal Properties:
Now let’s look at currents that run parallel to the axis of the cable. These are called longitudinal
currents which we will denote by the symbol Ia . Now that we want to look at currents down the fiber,
we need to locate at what position we are on the fiber. We will let the variable z denote the cable
position and we will assume to cable has length L. We show this situation in Figure 9.4.
The surface area of each endcap of the cable cylinder is πa2 . This implies that if we cut the
cable perpendicular to its longitudinal axis, the resulting slice will have cross-sectional area πa2 . Our
currents are thus:
• Ia is the longitudinal current flow which has units of amps.
amps
• Ja is the longitudinal current flow density which has units of amps per unit area – cm2
.
with the usual conversion
Ia = πa2 Ja
Since the inside of the cable as being filled with a conducting fluid, we also know
Ja = σe E
145
and so
Ia = πa2 σe E
πa2 E
=
ρ
using the definition of resistivity. From standard physics, it follows that
dΨ
E = −
dz
where Ψ is the potential in the conductor. Hence, we have
ρIa dΨ
2
= −
πa dz
implying
V = Ψ(L) − Ψ(0)
ρIa
= L
πa2
Now if we use Ohm’s law to relate potential, current and resistance as usual, we would expect a
relationship of the form
V = Resistance Ia
ρL
= Ia
πa2
This suggests that the term in front of Ia plays the role of a resistance. Hence, we will define R to be
146
(a) Cable Membrane With Wall Thickness (b) The Detailed Cross Sec-
Shown tion
Figure 9.5: Adding Thickness To The Cable Wall
the resistance of the cable by
ρL
R =
πa2
R ρ
The resistance per unit length would then be r = L
which is πa2
. This notation is a bit unfortunate
as we usually use the symbol r in other contexts to be a resistance measured in ohms; here it is a
ohms
resistance per unit length measured in cm
. Note that the resistance per unit length here is of the
form Aρ .
9.4 Current in a Cable with a Thin Wall:
So far, we haven’t actually thought of the cable wall as having a thickness. Now let’s let the wall
thickness be ` and consider the picture shown in Figure 9.5(a). with exaggerated cross section as
shown in Figure 9.5(b).
We let the variable s indicate where we are at inside the membrane wall. Hence, s is a variable
which ranges from a value of 0 (the inner side of the membrane) to the value a + ` (the outer side of
the membrane). Let Ir denote the radial current as usual; then the radial current density is defined by
147
Ir
Jr (s) =
2πsL
Now following the arguments we used before, we know that Jr (s) = σe E and hence
Jr (s) dΨ
E = = −
σe ds
This implies
Ir dΨ
= −σe
2πsL ds
Integrating, we find
Z a+`
Ir Z Ψ(a+`)
dΨ
= −σe
a 2πsL Ψ(a) ds
!
Ir a+`
ln = −σe (Ψ(a + `) − Ψ(a))
2πL a
Now Ψ(a + `) (Vout ) is the voltage outside the cable at the end of the cell wall and Ψ(a) (Vin ) is the
voltage inside the cable at the start of the cell wall. As usual, we represent the potential difference
Vin − Vout by Vr . Thus, using the definition of ρ, we have
!
a+` 2πLσe Vr
ln =
a Ir
2πL Vr
=
ρIr
We conclude
148
ρIr `
Vr = ln(1 + )
2πL a
Recall that ` is the thickness of the cell wall which in general is very small compared to the radius a.
Hence the ratio of ` to a is usually quite small. Recall from basic calculus that for a twice differentiable
function f defined near the base point x0 that we can replace f near x0 as follows:
1 00
f (x) = f (x0 ) + f 0 (x0 )(x − x0 ) + F (c)(x − x0 )2
2
where the number c lies in the interval (x0 , x). Unfortunately, this number c depends on the choice of
x, so this equality is not very helpful in general. The straight line L(x, x0 ) given by
L(x, x0 ) = f (x0 ) + f 0 (x0 )(x − x0 )
is called the tangent line approximation or first order approximation to the function f near x0 . Hence,
we can say
1 00
f (x) = L(x, x0 ) + F (c)(x − x0 )2
2
This tells us the error we make in replacing f by its first order approximation, e(x, x0 ), can be defined
by
e(x, x0 ) = |f (x) − L(x, x0 )|

1 00
= |F (c)|(x − x0 )2
2
149
Now ln(1 + x) is two times differentiable on (0, ∞) so we have the first order approximation to
ln(1 + x) near the base point 0 is given by
1
L(x, x0 ) = ln(1) + |x=0 (x − 0)
1+x
= x
with error
e(x, 0) = | ln(1 + x) − x|
1 1
= x2
2 (1 + c)2
where c is some number between 0 and x. Even though we can’t say for certain where c is in this
interval, we can say that
1
≤ 1
(1 + c)2
no matter what x is! Hence, the error in making the first order approximation on the interval [0, x] is
always bounded above like so
1 2
e(x, 0) ≤ x
2
`
Now for our purposes, let’s replace ln(1 + a
) with a first order approximation on the interval (0, a` ).
`
Then the x above is just a
and we see that the error we make is
1 ` 2
e(x, 0) ≤ ( )
2 a
150
If the ratio of the cell membrane to radius is small, the error we make is negligible. For example,
a biological membrane is about 70 nM thick and the cell is about 20, 000 nM in radius. Hence the
membrane to radius ration is 3.5e − 3 implying the error is on the order of 10−5 which is relatively
small. Since in biological situations, this ratio is small enough to permit a reasonable first order
`
approximation with negligible error, we replace ln(1 + a
) by a` . Thus, we have to first order
ρIr `
Vr =
2πL a
Vr ρ`
R = =
Ir 2πLa
We know R is measured in ohms and so the resistance R of the entire cable at the inner wall is R times
the inner surface area of the cable which is 2πLa. Hence, R = ρ` which has units of ohms − cm2
and the resistance per unit length. We know the wall has an inner and an outer surface area. The
`
outer surface area is 2πa(1 + a
)L which is a bit bigger. In order to define the resistance of a unit
surface area, we need to know which surfaced area we are talking about. So here, since we have
already approximated the logarithm term around the base point 0 (which means the inside wall as
1 + 0 corresponds to the inside wall!) we choose to use the surface area of the inside wall. Note how
there are many approximating ideas going on here behind the scenes if you will. We must always
remember these assumptions in the models we build!
The upshot of all of this discussion is that for a cable model with a thin membrane, the resistance per
ohms
unit length , r, with units cm
, should be defined to be
R ρ
r = =
` 2πLa
151
152
Chapter 10
The Cable Model:
In a uniform isolated cell, the potential difference across the membrane depends on where you are
on the cell surface. For example, we could inject current into a cylindrical cell at position z0 as
shown in Figure 10.2(a). In fact, in the laboratory , we could measure the difference between V m (the
membrane potential) and V0m (the rest potential) that results from the current injection at z = 0 at
various positions z downstream and we would see potential difference curves vs. position that have
the appearance of Figure 10.1.
1
The z = 0 curve is what we would measure at the site of the current injection; the z = 2
and z = 2
1
curves are what we would measure 2
or 2 units downstream from the injection site respectively. Note
the spike in potential we see is quite localized to the point of injection and falls rapidly off as we move
to the right or left away from the site. Our simple cylindrical model gave us
ρIr `
Vr =
2πLa
as the voltage across the membrane or cell wall due to a radial current Ir flowing uniformly radially
across the membrane along the entire length of cable. So far our model do not allow us to handle
dependence on position so we can’t reproduce voltage vs position curves as shown in Figure 10.1. We
also currently can’t model explicit time dependence in our models!
Now we wish to find a way to model V m as a function of the distance downstream from the current
153
Figure 10.1: Potential Difference vs Position Curves
injection site and the time elapsed since the injection of the current. This model will be called the
Core Conductor Model .
10.1 The Core Conductor Model Assumptions:
Let’s start by imagining our cable as a long cylinder with another cylinder inside it. The inner cylinder
has a membrane wall of some thickness small compared to the radius of the inner cylinder. The outer
cylinder simply has a skin of negligible thickness. If we take a radial cross section as shown in Figure
10.2(b) we see
In this radial cross section, let’s label the important currents and voltages as shown in Figure
10.3(a). As you can see, we are using the following conventions:
• t is time usually measured in milli-seconds or mS.
• z is position usually measured in cm.
• (r, θ) are the usual polar coordinates we could use to label points in any given radial cross
section.
• Ke (z, t) is the current per unit length across the outer cylinder due to external sources applied in
154
(a) Current Injection (b) Radial Cross Section
Figure 10.2: Cylindrical Cell Details
a cylindrically symmetric fashion. This will allow us to represent current applied to the surface
amp
through external electrodes. This is usually measured in cm
• Km (z, t) is the membrane current per unit length from the inner to outer cylinder through the
amp
membrane. This is also measure in cm
.
• Vi (z, t) is the potential in the inner conductor measured in milli-volts or mV.
• Vm (z, t) is the membrane potential measured in milli-volts or mV.
• Vo (z, t) is the potential in the outer conductor measured in milli-volts or mV.
We can also look at a longitudinal slice of the cable as shown in Figure 10.3(b)
The longitudinal slice allows us to see the two main currents of interest, Ii and Io as shown in
Figure 10.4, we see
where
• Io (z, t) is the total longitudinal current flowing in the +z direction in the outer conductor mea-
sured in amps.
• Ii (z, t) is the total longitudinal current flowing in the +z direction in the inner conductor mea-
sured in amps.
The Core Conductor Model is built on the following assumptions:
155
(a) Currents and Voltages in the Ra- (b) A Longitudinal Slice of the Cable
dial Cross Section
Figure 10.3: Radial and Longitudinal Details
Figure 10.4: Longitudinal Currents
156
1. The cell membrane is a cylindrical boundary separating two conductors of current called the in-
tracellular and extracellular solutions. We assume these solutions are homogeneous , isotropic
and obey Ohm’s Law .
2. All electrical variables have cylindrical symmetry which means the variables do not depend on
the polar coordinate variable θ.
3. A circuit theory description of currents and voltages is adequate for our model.
4. Inner and outer currents are axial or longitudinal only. Membrane currents are radial only.
5. At any given position longitudinally (i.e. along the cylinder) the inner and outer conductors are
equipotential . Hence, potential in the inner and outer conductors is constant radially . The only
radial potential variation occurs in the membrane.
Finally, we assume the following geometric parameters:
ohm
• r0 is the resistance per unit length in the outer conductor measured in cm
.
ohm
• r0 is the resistance per unit length in the inner conductor measured in cm
.
• a is the radius of the inner cylinder measured in cm.
It is also convenient to define the current per unit area variable Jm :
amp
• Jm (z, t) is the membrane current density per unit area measured in cm2
.
10.2 Building the Core Conductor Model:
Now let’s look at a slice of the model between positions z − ∆z and z + ∆z. In Figure 10.5, we see
one half of the full model that stretches a full 2∆z in length.
From the 2∆z slice in Figure 10.5, we can abstract the electrical network model we see in Figure
10.6:
Now in the inner conductor, we have current Ii (z, t) entering the face of the inner cylinder. At
that point the inner cylinder is at voltage Vi (z, t). A distance ∆z away, we see current I(z + ∆z, t)
157
Figure 10.5: The Two Slice Model
Figure 10.6: The Equivalent Electrical Network Model
158
Figure 10.7: Inner Cylinder Currents
leaving the cylinder and we note the voltage of the cylinder is now at V (z + ∆z, t). Finally, there is
a radial membrane current coming out of the cylinder uniformly all through this piece of cable. We
illustrate this in Figure 10.7:
Now we know that the total current I through the membrane is given by
I(z, t) = 2πa Jm (z, t) ∆z
= Km (z, t) ∆z
and at Node d , from Kirchoff’s Law the currents going into the node should match the currents
coming out of the node:
Io (z, t) + Km (z, t) ∆z = Io (z + ∆z, t) + Ke (z, t) ∆z
Also, the voltage drop across the resistance ri ∆z between Node a and Node b satisfies
ri ∆z Ii (z + ∆z, t) = Vi (z, t) − Vi (z + ∆z, t)
Similarly, between Node d and Node c we find the voltage drop satisfies
159
ro ∆z Io (z + ∆z, t) = Vo (z, t) − Vo (z + ∆z, t)
Also at Node a , we find
Ii (z, t) − Km (z, t) ∆z = Ii (z + ∆z, t)
Next, note that Vm is Vi − Vo . Now we know that the inner current per unit area density is Ji and it
is defined by
Ii (s, t)
Ji (s, t) =
πa2
= σi Ei
dΨ
= −σi
ds
where s is the position in the inner cylinder, σi is the conductivity and Ei is the electrical field density
per length of the inner solution, respectively and Ψ is the potential at position s in the inner cylinder.
It then follows that
Ii (s, t)
= −dΨ
πa2 σi
implying
Ii (s, t)
ds = −dΨ
πa2 σi
Now let’s assume the inner longitudinal current from position z to position z + ∆z is constant with
160
value I(z, t). Then, integrating we obtain
Z z+∆z
Ii (z, t)
∆z = − dΨ
πa2 σi z
= Ψ(z) − Ψ(z + ∆z)
= Vi (z, t)
Finally, noting the resistivity of the inner solution, ρi , is the reciprocal of the conductivity, our ap-
proximation allows us to say
ρi Ii (z, t)
∆z = Vi (z, t)
πa2
This implies that resistance of this piece of cable can be modeled by
Vi (z, t) ρi ∆z
Ri (z, t) = =
Ii (z, t) πa2
and so we conclude that since Ri must be the same as ri ∆z, we have
ρi
ri =
πa2
Rearranging the relationships we have found, we summarize as follows:
Ii (z + ∆z, t) − Ii (z, t)
= −Km (z, t)
∆z
Io (z + ∆z, t) − Io (z, t)
= Km (z, t) − Ke (z, t)
∆z
Vi (z + ∆z, t) − Vi (z, t)
= −ri Ii (z + ∆z, t)
∆z
161
Vo (z + ∆z, t) − Vo (z, t)
= −ro Io (z + ∆z, t)
∆z
Now from standard calculus, we know that is a function f (z, t) has a partial derivative at the point
(z, t), then the following limit exists
f (z + ∆z, t) − f (z, t)
lim
∆z→0 ∆z
∂f
and the value of this limit is denoted by the symbol ∂z
. Now the equations above apply for any
choice of ∆z. Physically, we expect the voltages and currents we see here to be smooth differentiable
functions of z and t. Hence, we expect that if we let ∆z go to zero, we will obtain the equations:
∂Ii
= −Km (z, t) (10.1)
∂z
∂Io
= Km (z, t) − Ke (z, t) (10.2)
∂z
∂Vi
= lim (−ri Ii (z + ∆z, t))
∂z ∆z→0
= −ri Ii (z, t) (10.3)

∂Vo
= lim (−ro Io (z + ∆z, t))
∂z ∆z→0
= −ro Io (z, t) (10.4)
Vm = Vi − V0 (10.5)
We call Equations 10.1 - 10.2 the Core Equations . Note we can manipulate these equations as follows:
Equation 10.4 implies that
∂Vm ∂Vi ∂V0

= −
∂z ∂z ∂z
From Equations 10.3 and 10.4, it then follows that
162
∂Vm
= −ri Ii + ro Io
∂z
Thus, using Equations 10.1 and 10.2, we find
∂ 2 Vm ∂Ii ∂I0
2
= −ri + ro
∂z ∂z ∂z
= r i Km + r o Km − r o Ke
Thus, the core equations imply that the membrane voltage satisfies the partial differential equation
∂ 2 Vm
= (ri + ro )Km − ro Ke (10.6)
∂z 2
Note that the units here do work out. The second partial derivative of Vm with respect to z involves
ratios of first order partials of Vm with respect to z. The first order terms, by the definition of the
volt volt
partial derivative, have units of cm
; hence, the second order terms have units of cm2
. Each of the ri
ohm amps
or rO terms have units cm
and the Km or Ke are current per length terms with units cm
. Thus the
amp−ohm volt
products have units cm2
or cm
. This partial differential equation is known as the Core Conductor
Equation .
163
164
Chapter 11
The Transient Cable Equations:
Normally, we find it useful to model stuff that is happening in terms of how far things deviate or move
away from what are called nominal values. We can use this idea to derive a new form of the Core
Conductor Equation which we will call the Transient Cable Equation . Let’s denote the rest values of
voltage and current in our model by
• Vm0 is the rest value of the membrane potential.
0
• Km is the rest value of the membrane current per length density.
• Ke0 is the rest value of the externally applied current per length density.
• Ii0 is the rest value of the inner current.
• Io0 is the rest value of the inner current.
• Vi0 is the rest value of the inner voltage.
• Vo0 is the rest value of the inner voltage.
It is then traditional to define the transient variables as perturbations from these rest values using the
same variables but with lower case letters:
• vm is the deviation of the membrane potential from rest.
• ii is the deviation of the current in the inner fluid from rest.
165
• io is the deviation of the current in the outer fluid from rest.
• vi is the deviation of the voltage in the inner fluid from rest.
• vo is the deviation of the voltage in the outer fluid from rest.
• km is the deviation of the membrane current density from rest.
These variables are defined by
vm (z, t) = Vm (z, t) − Vm0
vi (z, t) = Vi (z, t) − Vi0
vo (z, t) = Vo (z, t) − Vo0

0
km (z, t) = Km (z, t) − Km
ii (z, t) = Ii (z, t) − Ii0
io (z, t) = Io (z, t) − Io0
11.1 Deriving the Transient Cable Equation:
Now in our core conductor model so far, we have not modeled the membrane at all. For this transient
version, we need to think more carefully about the membrane boxes we showed in Figure 10.6. We
will replace our empty membrane box by a parallel circuit model. Now this box is really a chunk of
membrane that is ∆z wide. We will assume our membrane has a constant resistance and capacitance.
We know that conductance is reciprocal resistance, so our model will consist to a two branch circuit:
one branch is contains a capacitor and the other, the conductance element. We will let cm denote the
f ahrad
membrane capacitance density per unit length (measured in cm
). Hence, in our membrane box, the
since the box is ∆z wide, we see the value of capacitance should be cm ∆z. Similarly, we let gm be
1
the conductance per unit length (measured in ohm−cm
) for the membrane. The amount of conductance
for the box element is thus gm∆z. In Figure 11.1, we illustrate our new membrane model. Since this
is a resistance - capacitance parallel circuit, it is traditional to call this an RC membrane model .
166
Figure 11.1: The RC Membrane Model
In Figure 11.1, the current going into the element is Km (z, t)∆z and we draw the rest voltage for the
membrane as a battery of value Vm0 .
What happens when the membrane is at rest? At rest, all of the transients must be zero. At rest,
there can be no capacitative current and so all the current flows through the conductance branch. Thus
applying Ohm’s law,
0
Km (z, t) ∆z = gm ∆z Vm0 (11.1)
On the other hand, when we are not in a rest position, we have current through both branches. Recall
that the for a capacitor C, the charge q held in a capacitor due to a voltage V is q = CV which
dq
implies that the current through the capacitor due to a time varying voltage is i = dt
given by
∂V
i = C
∂t
From Kirchhoff’s voltage law, we see
167

0
∂ 0
Km + km (z, t) ∆z = gm ∆z Vm0 + vm (z, t) cm ∆z + Vm + vm (z, t)
∂t
Using Equation 11.1 and taking the indicated partial derivative, we simplify this to
∂vm
km (z, t) ∆z = gm ∆z vm (z, t) + cm ∆z
∂t
Upon canceling the common ∆z term, we find the fundamental identity
∂vm
km (z, t) = gm vm (z, t) + cm (11.2)
∂t
Now the core conductor equation in terms of our general variables is
∂ 2 Vm
= (ri + ro )Km − ro Ke
∂z 2
∂2
(V 0 + vm (z, t) = (ri + ro )(Km
0
+ km (z, t)) − ro (Ke0 + ke (z, t))
∂z 2 m
Thus, in terms of transient variables, we have
∂ 2 vm 0
2
= (ri + ro )Km + −ro Ke0 + (ri + ro )km − ro ke
∂z
This leads to
∂ 2 vm 0
− (ri + ro )km + ro ke = (ri + ro )Km − ro Ke0
∂z 2
168
Now at steady state, both sides of the above equation must be zero. This gives us the identities:
∂ 2 vm
= (ri + ro )km − ro ke
∂z 2
0
(ri + ro )Km = ro Ke0
However, Equation 11.2, allows us to replace km by an equivalent relationship. We obtain
∂ 2 vm ∂vm
2
= (ri + ro )(gm vm + cm ) − ro ke
∂z ∂t
0
(ri + ro )Km = ro Ke0
The Transient Cable Equation or just Cable Equation is then
∂ 2 vm ∂vm
2
− (ri + ro )cm − (ri + ro )gm vm = −ro ke (11.3)
∂z ∂t
11.2 The Space and Time Constant of a Cable:
The Cable Equation 11.3 can be further rewritten in terms of two new constants, the space constant of
the cable, λc , and the time constant, τm . Note, we can rewrite 11.3 as
1 ∂ 2 vm cm ∂vm ro
2
− − vm = − ke
(ri + ro )gm ∂z gm ∂t (ri + ro )gm
Define the new constants
s
1
λc =
(ri + ro )gm
169
cm
τm =
gm
Then
ro
= ro λ2c
(ri + ro )gm
and the Cable Equation 11.3 can be written in a new form as
∂ 2 vm ∂vm
λ2c 2
− τm − vm = −ro λ2c ke (11.4)
∂z ∂t
The new constants τm and λc are very important to understanding how the solutions to this equation
will behave. We call τm the time constant and λc the space constant of our cable.
cm
The Time Constant τm : Consider the ratio gm
. Note that the units of this ratio are f ahrad − ohm.
Recall that charge deposited on a Capacitor of value C fahrads is q = CV where V is the voltage
across the capacitor. Hence, a dimensional analysis shows us that coulombs equal fahrad-volts.
But we also know from Ohm’s law that voltage is current times resistance; hence, dimensional
coulomb−ohm coulomb
analysis tells us that volts equal sec
. We conclude that f ahrad − ohm equals volt
coulomb sec
times ohm. But a volt
is a ohm
by Ohm’s law as discussed above. Hence, simplifying, we
cm
see the ration gm
has unit of seconds. Hence, this ratio is a time variable. This is why we define
this constant to be the Time Constant of the cable, τm . Note that τm is a constant whose value
is independent of the size of the cell; hence it is a membrane property .
Also, if we let Gm be the conductance of a square centimeter of cell membrane. Then Gm has
1
units of ohm−cm2
. The conductance of our ∆z box of membrane in our model was gm ∆z and
the total conductance of the box is also Gm times the surface area of the box or Gm 2πa ∆z.
Equating expressions, we see that
170
gm = 2πa Gm
In a similar manner, if Cm is the membrane capacitance per unit area, we have
cm = 2πa Cm
Cm
We see the time constant can thus be expressed as Gm
also.
1
The Space Constant λc : Consider the dimensional analysis of the term (ri +ro )gm
. The sum of the
ohm 1
resistances per length have units cm
and gm has units ohm−cm
. Hence, the denominator of this
fraction has units ohm
cm
times 1
ohm−cm
or cm−2 . Hence, this ratio has units of cm2 . This is why the
square root of the ratio functions as a length parameter. Now in Chapter 9, we looked carefully
at how to define the notion of resistance for a longitudinal flow. Applying this to the inner flow
in our cable, we see
ρi
ri =
πa2
Now in biological settings, we typically have that ri is very large compared to ro . Hence, the
term ri + ro is nicely approximated by just ri . In this case, since gm is 2πa Gm , we see
s
1
λc =
ri gm
v
1
u
u
= t ρi
πa2
2πaGm
s
a
=
2ρi Gm
171
Now ρi and Gm are membrane constants independent of cell geometry. So we see that the space
constant is proportional to the square root of the fiber radius . Note also that the space constant
decreases as the fiber radius shrinks.
172
Chapter 12
Time Independent Solutions to the Cable

Equation:
In Figure 12.1, we see a small piece of cable as described in Chapter 9. We are injecting current Ie
into the cable via an external current source at z = 0. We assume the current that is injected in
uniformly distributed around the cable membrane.
12.1 The Infinite Cable:
We will begin by assuming that the cable extends to infinity both to the right and to the left of the
current injection site. This is actually easier to handle mathematically, although you will probably
Figure 12.1: Current Injection Into a Cable
173
find it plenty challenging! The picture we see in Figure 12.1 is thus just a short piece of this infinitely
long cable. Now if a dendrite or axon was really long, this would probably not be a bad model, so
there is a lot of utility in examining this case as an approximation to reality. We also assume the other
end of the line that delivers the current Ie is attached some place so far away it has no effect on our
cable.
The time dependent cable equation is just the full cable equation 11.4 from Chapter 11. Recall that ke
is the external current per unit length. Hence, λc ke is a current which is measured in amps. We also
know that λc ro is a resistance measured in ohms. Hence, the product ro λc times λc ke is a voltage as
from Ohm’s law, resistance times current is voltage. Thus, the right hand side of the cable equation is
the voltage due to the current injection. On the left hand side, a similar analysis shows that each term
represents a voltage.
∂ 2 vm volt
• λ2c ∂z 2
is measured in cm2 times cm2
or volts.
∂vm volt
• τm ∂t
is measured in seconds times second
or volts.
• vm is measured volts.
∂vm
Now if we were interested only in solutions that did not depend on time, then the term ∂t
would be
zero. Also, we could write all of our variables as position dependent only; i.e. vm (z, t) as just vm (z)
and so on. In this case, the partial derivatives are not necessary and we obtain an ordinary differential
equation:
d2 vm
λ2c 2
− vm (z) = −ro λ2c ke (z) (12.1)
dz
12.2 Solving the Time Independent Infinite Cable Equation:
Equation 12.1 as written does not impose any boundary or initial conditions on the solution. Even-
tually, we will have to make a decision about these conditions, but for the moment, let’s solve this
general differential equation as it stands. The typical solution to such an equation is written in two
174
parts: the homogeneous part and the particular part. The homogeneous part or solution is the
function φh that solves
d2 vm
λ2c − vm (z) = 0 (12.2)
dz 2
This means that if we plug φh into 12.2, we would find
d2 φh
λ2c − φh (z) = 0
dz 2
The particular part or solution is any function φp that satisfies the full equation 12.1; i.e.
d2 φp
λ2c − φp (z) = −ro λ2c ke (z)
dz 2
It is implied in the above discussions that φh and φp must be functions that have two derivatives for
all values of z that are interesting. Since this first case concerns a cable of infinite length, this means
here that φh and φp must be twice differentiable on the entire z axis. We can also clearly see that
adding the homogeneous and particular part together will always satisfy the full time dependent cable
equation. Let φ denote the general solution. Then
φ(z) = φh (z) + φp (z)
and φ will satisfy the time independent cable equation. If the external current ke is continuous in z,
then since the right hand side must equal the left hand side, the continuity of the right hand side will
force the left hand side to be continuous also. This will force the solution φ we seek to be continuous
in the second derivative. So usually we are looking for solutions that are very nice: they are continuous
in the second derivative. This means that there are no corners in the second derivative of voltage.
175
12.2.1 Solving the Homogeneous Equation:
The standard way to solve the homogeneous equation is to assume the solution φh has the form erz .
Plugging this into the homogeneous equation and taking the needed derivatives, we find the factored
form

λ2c r2 − 1 erz = 0
Since this equation must hold for all z and the exponential term is never zero, we must have the term
in parenthesis is zero. Thus
λ2c r2 − 1 = 0
This is called the characteristic or auxiliary equation of the homogeneous equation. This is a simple
quadratic equation which has the roots
1
r+ =
λc
1
r− = −
λc
+z −z
From what we have said above, we see that the functions er and er are both homogeneous solu-
+z −
tions in the sense we have mentioned. Thus, any combination of the form A1 er + A2 er z , for real
numbers A1 and A2 , will also work. Thus, the homogeneous solution we seek is
z z
φh (z) = A1 e λc + A2 e− λc (12.3)
176
12.2.2 Solving the Non-homogeneous Equation:
Since we don’t know the explicit function ke we wish to use in the non-homogeneous equation, the
common technique to use to find the particular solution is the one called Variation of Parameters . In
this technique, we take the homogeneous solution and replace the constants A1 and A2 by unknown
functions U1 (z) and U2 (z). Then we see if we can derive conditions that the unknown functions U1
and U2 must satisfy in order to work.
So we start by assuming
z z
φp (z) = U1 (z)e λc + U2 (z)e− λc
Using the chain and product rule for differentiation, the first derivative of φp gives:
dφp dU1 λz 1 z dU2 − λz

= e c + U1 (z) e λc + e c
dz dz λc dz
1 z dU1 z dU2 − λz
− U2 (z) e− λc e λc + e c
λc dz dz
1 z 1 z
+ U1 (z) e λc − U2 (z) e− λc
λc λc
The theory of ordinary differential equations forces us to impose the first condition:
dU1 λz dU2 − λz
e c + e c = 0
dz dz
This simplifies the first derivative of φp to be
dφp 1 z 1 z
= U1 (z) e λc − U2 (z) e− λc
dz λc λc
Now take the second derivative to get
177
dφp dU1 1 λz dU2 1 − λz

= e c − e c
dz dz λc dz λc
1 z 1 z
+ U1 (z) 2 e λc + U2 (z) 2 e− λc
λc λc
Now plug these derivative expressions into the non-homogeneous equation to find
dU1 1 λz dU2 1 − λz
−ro λ2c ke (z) = λ2c e c − e c
dz λc dz λc
!
1 λz 1 − λz
+ U1 (z) 2 e c + U2 (z) 2 e c
λc λc
z z
− U1 (z)e λc + U2 (z)e− λc
Now
!
1 z 1 z
0 = λ2c U1 (z) 2 e λc + U2 (z) 2 e− λc
λc λc
z z
− U1 (z)e λc + U2 (z)e− λc
so all of this reduces to
e c − e c = −ro ke (z)
dz λc dz λc
This gives us a second condition on the unknown functions U1 and U2 . Combining we have
dU1 λz dU2 − λz
e c + e c = 0
dz dz
e c − e c = −ro ke (z)
dz λc dz λc
178
This can be rewritten in a matrix form:
     
z
− λz dU1
 e λc e c   dz   0 
    =  
1 λzc z
− λ1c e− λc
     
dU2
λc
e dz
−ro ke
We can user Cramer’s Rule to solve for the unknown functions U10 and U20 where the superscript
indicates the derivative with respect to z. Let W denote the matrix
 
z
− λz
 e λc e c 
W =  z

− λz
 
1
λc
e λc − λ1c e c
Then the determinant of W is det(W ) = − λ2c and by Cramer’s Rule
 
− λz
dU1  0 e c
= (det(w))−1 det 


dz 
1 − λzc
−ro ke − λc e

z
ro ke e− λc
=
− λ2c
ro λc − λz
= − ke e c
2
and
 
z
dU2  e λc 0
= (det(w))−1 det 


dz 
1 λzc
e −ro ke

λc
z
−ro ke e λc
=
− λ2c
ro λc z
= k e e λc
2
Thus, integrating,
179
r 0 λc Z z u
U1 (z) = − ke (u) e− λc du
2 0
r0 λc Z z u
U2 (z) = ke (u) e λc du
2 0
where 0 is a convenient starting point for our integration. Hence, the particular solution to the non-
homogeneous time independent infinite cable equation is
z z
φp (z) = U2 (z) e− λc + U1 (z) e λc
! !
r0 λc Z z u
− λz r0 λc Z z u z
φp (z) = ke (u) e du e
λ c c − ke (u) e− λc du e λc
2 0 2 0
Z z Z z
r0 λc u−z r 0 λc u−z
= ke (u) e λc du − ke (u) e− λc du
2 0 2 0
and the general solution is thus
− λz z r 0 λc Z z u−z r 0 λc Z z u−z
φ(z) = A2 e c + A1 e λc + ke (u) e c du −
λ ke (u) e− λc du
2 0 2 0
for any real constants A1 and A2 .
We can rewrite this as
− λz z r0 λc − λz Z z u r0 λc λz Z z u
φ(z) = A2 e c + A1 e λc + e c ke (u) e c du −
λ e c ke (u) e− λc du
2 0 2 0
u
Finally, making the change of variable v = λc
, we have
z z
− λz z r0 λ2c − λz Z λc r0 λ2c λz Z λc
φ(z) = A2 e c + A1 e λc + e c v
ke (λc v) e dv − e c ke (λc v) e−v dv
2 0 2 0
180
12.3 Modeling Current Injections:
We are interested in understanding what the membrane voltage solution should look like in the event
of a current injection at say z = 0 for a very short period of time. We could then use this idealized
solution to understand the response of the cable model to current injections occurring over very brief
time periods of various magnitudes at various spatial locations.
First, let’s make our equations easier to understand by explicitly taking advantage of the space constant
λc . Recall our differential equation is
d2 vm
λ2c − vm (z) = −ro λ2c ke (z)
dz 2
z
If we make the change of variable y = λc
, we have λc dy = dz and so by the chain rule for
differentiation
dv m dv m dz
=
dy dz dy
dv m
= λc
dz
d2 v m d dv m dy
=
dy 2 dz dy dz
d dv m
= (λc ) λc
dz dz
d2 v m
= λ2c
dz 2
Hence, our differential equation becomes
d2 vm
− vm (λc y) = −ro λ2c ke (λc y)
dy 2
The general solution is
181
−y r0 λ2c −y Z y r0 λ2c y Z y
φ(λc y) = A2 e y
+ A1 e + e v
ke (λc v) e dv − e ke (λc v) e−v dv
(12.4)
2 0 2 0
Now what we done above is valid for any external current injection. Now let’s specialize as follows:
we assume
• The current injection ke is symmetric about 0.
• The current ke (λv) is zero on (−∞, −λc w) ∪ (λc w, ∞) for some nonzero w. Note then the
variable w is measured in terms of space constants so that λc w gives actual z distance.
• The current smoothly varies to zero at w and −w; i.e. ke is at least differentiable on the v axis.
R λc w
• The area under the curve, which is the current applied to the membrane, −λc w ke (u)du is I.
Given this type of current injection, we see we are looking for a solution to the problem

0 y < −w





2
d vm


− vm (λc y) = −ro λ2c ke (λc y) −w ≤ y ≤ w
dy 2 



 0 w < y


This amounts to solving three differential equations and then recognizing that the total solution is the
sum of the three solutions with the condition that the full solution is smooth at the points −w and w
where the solutions must connect. Now we know that membrane voltages are finite. In the first and
third region we seek a solution, we are simply solving the homogeneous equation. We know then the
solution is of the form Cey + De−y in both of these regions. However, in the (−inf ty, w) region,
the finiteness of the potential means that the Cey solution is the only one possible and in the (w, ∞)
region, the only solution is therefore of the form De−y . In the middle region, the solution is given by
the general solution we found from the Variation of Parameters method. Thus, we seek a solution of
the form
182

Cey y < −w







r0 λ2c r0 λ2c
 Ry Ry
 A2 e−y + A1 ey + e−y ke (λc v) ev dv − ey ke (λc v) e−v dv


2 0 2 0
φ(λc y) =
−w ≤ y ≤ w








 De−y w < y


Our solution and its derivative should be continuous at w and −w. We can easily compute the deriva-
tive of the solution to be
0 −y r0 λ2c −y Z y r0 λ2c y Z y
φ (λc y) = −A2 e + A1 e −y
e v
ke (λc v) e dv − e ke (λc v) e−v (12.5)
dv
2 0 2 0
Continuity in the solution at the points −w and w gives:
r0 λ2c w Z −w r0 λ2c −w Z −w
Ce−w = A2 ew + A1 e−w + e ke (λc v) ev dv − e ke (λc v) e−v dv
2 0 2 0
r0 λ2c −w Z w r0 λ2c w Z w
De−w = A2 e−w + A1 ew + e v
2 0 2 0
and continuity in the derivative at these points gives:
−w −w r0 λ2c w Z −w r0 λ2c −w Z −w
Ce = −A2 e w
+ A1 e − e v
2 0 2 0
r0 λ2c −w Z w r0 λ2c w Z w
−De−w = −A2 e−w + A1 ew − e ke (λc v) ev dv − e ke (λc v) e−v dv
2 0 2 0
To simplify the exposition, define
r0 λ2c Z w
J1+ = ke (λc v) e−v dv
2 0
r0 λ2c Z −w
J1− = ke (λc v) e−v dv
2 0
183
r0 λ2c Z w
J2+ = ke (λc v) ev dv
2 0
r0 λ2c Z −w
J2− = ke (λc v) ev dv
2 0
We can then rewrite our continuity conditions as
Ce−w = A2 ew + A1 e−w + ew J2− − e−w J1−
De−w = A2 e−w + A1 ew + e−w J2+ − ew J1+
Ce−w = −A2 ew + A1 e−w − ew J2− − e−w J1−
−De−w = −A2 e−w + A1 ew − e−w J2+ − ew J1+
This gives us the equations:
(C − A1 + J1− )e−w + (−A2 − J2− )ew = 0 (12.6)
(D − A2 − J2+ )e−w + (−A1 + J1+ )ew = 0 (12.7)
(C − A1 + J1− )e−w + (A2 + J2− )ew = 0 (12.8)
(−D + A2 + J2+ )e−w + (−A1 + J1+ )ew = 0 (12.9)
Computing the four new equations (12.6) - (12.8), (12.6) + (12.8), (12.7) - (12.9) and (12.7) + (12.9),
we find
(−2A2 − 2J2− )ew = 0
(2C − 2A1 + 2J1− )e−w = 0
(2D − 2A2 − 2J2+ )e−w = 0
(−2A1 + 2J1+ )ew = 0
184
Since the exponentials can never be zero, we have
−A2 − J2− = 0
C − A1 + J1− = 0
D − A2 − J2+ = 0
−A1 + J1+ = 0
Hence, the solution we seek is
A2 = −J2−
A1 = J1+
C = A1 − J1− = J1+ − J1−
D = A2 + J2+ = J2+ − J2−
Then the solution to this sort of current injection is thus

(J1+ − J1− ) ey y < −w







(−J2− e−y + J1+ ey ) + e−y
Ry Ry
φ(λc y) =
 0 ke (λc v) ev dv − ey 0 ke (λc v) e−v dv −w ≤ y ≤ w



 (J2+ − J2− ) e−y w < y


12.4 Modeling Instantaneous Current Injections:
We can perform the analysis we did in the previous section for any pulse of that form. Now let’s look
at a family of pulses ken which have the properties: for each positive integer n
• The current injection ken is symmetric about 0.
• The current ken (λv) is zero on (−∞, − λcnw ) ∪ ( λcnw , ∞) for some nonzero w. As usual, the
185
variable w is measured in terms of space constants. Let wn denote the fraction wn .
• The current smoothly varies to zero at wn and −wn ; i.e. ken is differentiable on the v axis.
R λc wn
• The area under the curve, which is the current applied to the membrane, −λc wn ke (u)du is I
for all n. This means that as the width of the symmetric pulse goes to zero, the height of the
pulse goes to infinity but in a controlled way: the area under the pulses is always the same
number I. So no matter what the base of the pulse, the same amount of current is delivered to
the membrane.
We let φn denote our solution:

+ −
(J1n − J1n ) ey y < −wn







φn (λc y) = − −y + y Ry Ry
 (−J2n e + J1n e ) + e−y 0 ke (λc v) ev dv − ey 0 ke (λc v) e−v dv −wn ≤ y ≤ wn



+ −
 (J2n − J2n ) e−y wn < y


where
r0 λ2c Z wn
+
J1n = ken (λc v) e−v dv
2 0
− r0 λ2c Z −wn
J1n = ken (λc v) e−v dv
2 0
+ r0 λ2c Z wn
J2n = ken (λc v) ev dv
2 0
− r0 λ2c Z −wn
J2n = ken (λc v) ev dv
2 0
Now to see what happens as we let n get larger and larger, we have to look at the limit as n goes to
infinity.
12.4.1 What Happens Away from 0?
Pick a point y0 that is not zero. Since y0 is not zero, there is a value of positive integer N so that y0 is
not inside the interval (−wN , wN ). Since wn gets smaller as n gets larger, this means that y0 is outside
186
of (−wn , wn ) for all n larger that N . Hence, either the first part or the third part of the definition of
φn applies. We will argue the case for y0 is positive which implies that the first part of the definition
is the one that is applicable. The case where y0 is negative would be handled in a similar fashion.
Since we assume that y0 is positive, we have for all n larger than N :
−
φn (λc y0 ) = (J2n
+
− J2n ) e−y0
I
What happens as n goes to ∞? We can prove that in the limit, we obtain λc
.
Lemma 1
4 +
lim J1n = I
n→∞ ro λc
4 −
lim J1n = −I
n→∞ r λ
o c
4 +
lim J2n = I
n→∞ r λ
o c
4 −
lim J2n = −I
n→∞ r λ
o c
Proof : It suffices to show this for just one of these four cases. We will show the first one: Consider

4 4 r λ2 Z w n
+ 0 c n −v
| J1n − I| = ke (λc v) e dv − I

ro λc ro λc 2 0
However, we know that the area under the curve is always I; hence for any n,
Z λc wn
I = ken (u)du
λc wn
Z wn
= λc ken (λc v)dv
−wn
Since our pulse is symmetric, this implies that
187
Z wn
I
= λc ken (λc v)dv
2 0
Substituting into our original expression, we find
Z wn Z wn
4

+
ken (λc v) e−v dv − 2λc ken (λc v)dv

| J1n − I| = 2λc
r o λc 0 0
Z wn
≤ 2λc ken (λc v) |e−v − 1|dv
0
Now we know that this exponential function is continuous at 0; hence, given I , there is a δ so that

|e−v − 1| < if |v| < δ
I
Since, wn goes to zero as n goes to ∞, we see that there is a positive integer N so that wn < δ when
n > N . Thus, for such n, we see our original expression can be overestimated by
4
Z wn

| J + − I| < 2λc ken (λc v) dv
ro λc 1n 0 I
But we know the other term in the above inequality is the constant area under the curves, I; we
conclude
4 +
| J1n − I| < I
ro λc I
=
4 +
This shows that the limit as n goes to infinity of ro λc
J1n is I.
QED
188
Hence, for y0 positive, we find
−
lim φn (λc y0 ) =
n→∞
+
lim (J2n
n→∞
− J2n ) e−y0
ro λc I ro λc I −y0
= ( + )e
4 4
ro λc I −y0
= e
2
In a similar fashion, for y0 negative, we find
−
lim φn (λc y0 ) =
n→∞
+
lim (J2n − J2n ) ey0
n→∞
ro λc I ro λc I −y0
= ( + )e
4 4
ro λc I −y0
= − e
2
12.4.2 What Happens at Zero?
When we are at zero, since 0 is in (−wn , wn ) for all n, we must use the middle part of the definition
of φn always. Now at 0, we see
Z 0 Z −0
− −0
φn (0) = −J2n + 0
e + J1n e + ken (λc v) ev dv − e0 ken (λc v) e−v dv
0 0
− +
= −J2n + J1n
From Lemma 1, we then find that
−
lim φn (0) =
n→∞
lim −J2n
n→∞
+
+ J2n
ro λc I ro λc I
= ( + )
4 4
ro λc I
=
2
189
Combining all of the above parts, we see we have shown that as n goes to infinity, the solutions φn
converge pointwise to the limiting solutionφ defined by
ro λc −|y|
φ(λc y) = Ie
2
or in terms of the original space variable z
r0 λc z
φ(z) = I e−| λc |
2
Now if the symmetric pulse sequence was centered at z0 with pulse width wn , we can do a similar
analysis (it is yucky though and tedious!) to show that the limiting solution would be
ro λc −|y−y0 |
φ(λc y) = Ie
2
or in terms of the original space variable z
r0 λc z−z0
φ(z) = I e−| λc |
2
12.5 Idealized Impulse Currents
Now as n gets large, our symmetric pulses are becoming very narrow base pulses of very large mag-
nitude. Clearly, these pulses are not defined in the limit as n goes to infinity as the limit process leads
to a mapping Iδ which should satisfy
Z ∞
Iδ (u)du = I
−∞
190
and the obviously nonsensical pointwise definition

 0 z 6= 0


Iδ (z) =
 ∞ z = 0


Think of Iδ as an amount of current I which is delivered instantaneously at z is 0. Of course, the only

way to really understand this idea is to do what we have done and consider a sequence of constant
current density pulses ken .
It is convenient to think of a unit idealized impulse called δ defined by

 0 z 6= 0


δ(z) = 
  ∞ z = 0
Z ∞
δ(u)du = 1
−∞
Then using this notation, we see that
Iδ = I δ
Moreover, if an idealized pulse is applied at z0 rather than 0, we can abuse this notation to define

 0 z 6= z0


δ(z − z0 ) =
 ∞ z = z0


Z ∞
δ(u − z0 )du = 1
−∞
and hence I δ(z − z0 ) is a idealized pulse applied at z0 .:
Note that the notion of an idealized pulse allows us to write the infinite cable model for an idealized
pulse applied at z0 of magnitude I in a compact form. We let the applied current density be ke (z) =
191
I δ(z − z0 ) giving us the differential equation
d2 vm
λ2c − vm (z) = −ro λ2c I δ(z − z0 )
dz 2
which we know has solution
r0 λc z−z0
φ(z) = I e−| λc |
2
In all of our analysis, we use a linear ordinary differential equation as our model. Hence, the linear
superposition principle applies and hence for N idealized pulses applied at differing centers and with
different magnitudes, the underlying differential equation is
N
d2 vm
λ2c 2
X
− vm (z) = −ro λc Ii δ(z − zi )
dz 2 i=0
with solution
N
r0 λc X z−zi
φ(z) = Ii e−| λc |
2 i=0
Note that the membrane voltage solution is a nonlinear summation of the applied idealized current
injections.
For example, let’s inject current of magnitudes I at 0 and 2I at λc respectively. The solution to the
1 2
current injection at 0 is vm and at λc , vm . Thus,
ro λc |z|
1
vm (z) = I e− λc
2
r o λc |z−λc |
2
vm (z) = 2I e− λc
2
192
Figure 12.2: Voltages Due to Two Current Impulses
We get a lot of information by looking at these two solutions in terms of units of the space constant λc .
If you look at Figure 12.2, you’ll see the two membrane voltages plotted together on the same access.
1 2
Now the actual membrane voltage is, of course, vm added to vm which we don’t show. However, you
can clearly see how quickly the peak voltages fall off as you move away from the injection site.
1
Note that one space constant away from an injection site z0 , the voltage falls by a factor of e
or 63%.
This is familiar exponential decay behavior.
12.6 The Inner and Outer Current Solutions:
Recall that the membrane current density km satisfies
∂vm
km (z, t) = gm vm (z, t) + cm
∂t
Here, we are interested in time independent solutions, so we have the simpler equation
193
km (z) = gm vm (z)
Thus, we have for an idealized current impulse injection at 0
r o λc |z|
km (z) = gm I e− λc
2
From our core conductor equations, we know that
∂Ii
= −Km (z)
∂z
and thus, using our transient variables
Io (z) = Io0 + i0 (z)
Ii (z) = Ii0 + ii (z)

0
Km (z) = Km + km (z)
we see that
∂ii 0
= −Km − km (z)
∂z
Integrating, we see
Z z
0
ii (z) = − (Km + km (u))du
−∞
194
0
We expect that the internal current is finite and this implies that the initial current density Km must
be zero as otherwise we obtain unbounded current. We thus have
Z z
ii (z) − ii (−∞) = − km (u)du
Z−∞
z
= − gm vm (u)du
−∞

Rz u
e λc z < 0

r o λc

 −∞
= − gm I R
2  0

 e
u
λc du +
Rz − λu
e c du z ≥ 0
−∞ 0
Also, for an impulse current applied at zero, we would expect that the inner current vanish at both
ends of the infinite cable. Hence, ii (−∞) must be zero. We conclude

u z

 λc e λc z−∞ = λc e λc z < 0

ro λc

ii (z) = − gm I 
2 u u z

 λc e λc 0−∞ − λc e− λc |z0 = λc (2 − e− λc )
 z ≥ 0
Using the definition of the space constant λc , we note the identity
ro
λ2c gm =
ri + r o
allowing us to rewrite the inner current solution as

 z
r o I  e λc z < 0

ii (z) = −
ri + ro 2  z
 (2 − e− λc )

z ≥ 0
Now, from Chapter 10, Equations 10.1) and (10.2), we know in our time independent case
∂Ii
= −Km (z)
∂z
195
∂Io
= Km (z) − Ke (z)
∂z
which implies
∂ii ∂io
+ = −Ke (z)
∂z ∂z
= −Ke0 − ke (z)
Integrating, we have
Z z ∂ii Z z
∂io Z z
du + du = − (Ke0 + ke (u))du
−∞ ∂z −∞ ∂z −∞
In order for this integration to give us finite currents, we see the constant Ke0 must be zero implying
Z z
ii (z) − ii (−∞) + io (z) − io (−∞) = − ke (u)du
−∞
We already know that ii is zero at z = −∞ for our idealized current impulse ke = Iδ(u). Further, we
know from our lengthy analysis of sequences of current pulses of constant area I, ken , that integrating
from −∞ to z > 0 gives I and 0 if z ≤ 0. Hence, the inner and outer transient currents for an
idealized pulse must satisfy

 −I z > 0


ii (z) + io (z) − io (−∞) =
 0 z ≤ 0


The argument to see this can be sketched as follows. If z is positive, for large enough n, the impulse
current ken is active on the interval [−λc wn , λc wn ] with λc wn less than z. So once we get past that
critical n, the integral becomes
196
Z λc wn
ken (u)du = I
−λc wn
On the other hand, if z is negative, eventually the interval where ken is non zero lies outside the region
on integration and so we get the value of the integral must be zero.
Physically, since we are using an idealized injected current, we expect that the outer current satisfies
io (−∞) is zero giving

 −I z > 0


ii (z) + io (z) = 
  0 z ≤ 0
We can rewrite our current solutions more compactly by defining the signum function sgn and the
unit step function u as follows:

 −1 z < 0


sgn(z) =
 +1 z ≥ 0



 0 z < 0


u(z) =
 1 z ≥ 0


Then we have
ro I

|z|
ii (z) = e− λc sgn(z) − 2u(z)
2(ri + ro )
Next, we can solve for io to obtain
io (z) = −Iu(z) − ii (z)
197
ro I

|z|
= −Iu(z) − e− λc sgn(z) − 2u(z)
2(ri + ro )
" #
ro ro I |z|
= −u(z) 1 − I − e− λc sgn(z)
2(ri + ro ) 2(ri + ro )
ri ro I |z|
= −u(z) I − e− λc sgn(z)
r i + ro 2(ri + ro )
This further simplifies to the final forms
ro I ri

|z|
io (z) = − e− λc sgn(z) − 2 u(z)
2(ri + ro ) ro
2
ro λ gm I − |z| ri

= − c e λc sgn(z) − 2 u(z)
2 ro
12.7 The Inner and Outer Voltage Solutions:
From Chapter 10, Equations 10.3) and (10.4), we see that for our time independent case
∂Vi
= −ri Ii (z)
∂z
∂Vo
= −ro Io (z)
∂z
Rewriting in terms of transient variables, we have
∂vi
= −ri [Ii0 + ii (z)]
∂z
∂vo
= −ro [Io0 + i0 (z)]
∂z
We expect our voltages to remain bounded and so we must conclude that Ii0 and Io0 are zero, giving
Z z
vi (z) − vi (−∞) = −ri ii (u)du
−∞
198
Z z
vo (z) − vo (−∞) = −ro io (u)du
−∞
To finish this step of our work, we must perform these messy integrations. They are not hard, but are
messy! After a bit of arithmetic, we find
ri ro Iλc z

|z|
vi (z) − vi (−∞) = e− λc + 2 u(z)
2(ri + ro ) λc
ro2 Iλc ri z

|z|
−λ
vo (z) − vo (−∞) = −e c + 2 u(z)
2(ri + ro ) r o λc
Finally, note that after a bit of algebraic magic
ro Iλc − |z|
vi (z) − vo (z) = vi (−∞) − vo (−∞) + e λc
2
Recall that vm is precisely the last term in the equation above; hence we have
vi (z) − vo (z) = vi (−∞) − vo (−∞) + vm (z)
The usual convention is that the voltages at infinity vanish; hence vi (−∞) and vo (−∞) are zero and
we have the membrane voltage solution we expect:
vi (z) − vo (z) = vm (z)
12.8 Summarizing The Infinite Cable Solutions:
We have shown that the solutions here are
199
ro λc I − |z|
vm (z) = e λc
2
ro λ2c gm I −|z|
ii (z) = ( e λc sgn(z) − 2u(z) )
2
ro λ2c gm I −|z| ri
io (z) = − ( e λc sgn(z) + 2 u(z) )
2 ro
3
ri ro λc gm I −|z| z
vi (z) = − ( e λc + 2 u(z) )
2 λc
ro2 λ3c gm I −|z| ri z
vo (z) = − (− e λc + 2 u(z) )
2 r o λc
vm (z) = vi (z) − vo (z)
where we assume vi and vo are zero at negative infinity. We can also write these is a normalized
form by noting that the parameter α describe earlier can be used to modify the equations above into a
dimensionless form.
Since λ2c can be expressed in terms of ri and ro , we have also shown that
ro λc I − |z|
vm (z) = e λc
2
ro I −|z|
ii (z) = ( e λc sgn(z) − 2u(z) )
2 (ri + ro )
ro I −|z| ri
io (z) = − ( e λc sgn(z) + 2 u(z) )
2 (ri + ro ) ro
ri r o I −|z| z
vi (z) = − ( e λc + 2 u(z) )
2 (ri + ro ) λc
ro2 I −|z| ri z
vo (z) = − (− e λc + 2 u(z) )
2 (ri + ro ) r o λc
12.9 Normalized Solutions:
Then we can normalize (and therefore remove most of the interesting physical content!) with the
change of variables:
200
Figure 12.3: Normalized Current Solutions
ri
α =
ro
z
λ =
λc
∗ 2
vm = vm
r o λc I
2
vi∗ = vi
r o λc I
2
vo∗ = vo
r o λc I
ii
i∗i =
I
ii
i∗o =
I
which leads to the solutions you see in Figure 12.3.
With this change of variables, the solutions to the cable equation can be written:
∗
vm (λ) = e − |λ|
201
1
i∗i (λ) = (e−|λ| sgn(λ) − 2 u(λ))
2 (α + 1)
−1
i∗o (λ) = (e−|λ| sgn(λ) + 2 u(λ))
2 (α + 1)
α
vi∗ (λ) = (e−|λ| + 2 λ u(λ))
(α + 1)
1
vo∗ (λ) = (− e−|λ| + 2 α λ u(λ))
(α + 1)
The behavior of these normalized solutions at 0 is interesting. Note
1
lim + i∗i = −
λc → 0 2(α + 1)
1
lim i∗i = −
λc → 0− 2(α + 1)
2α + 1
lim i∗o = −
λc → 0+ 2(α + 1)
1
lim i∗o =
λc → 0− 2(α + 1)
and the asymptotic values at ∞ and −∞ are given by
1
lim i∗i = −
λc → ∞ α+1
lim i∗i = 0
λc → −∞
α
lim i∗o = −
λc → ∞ α+1
lim i∗o = 0
λc → −∞
From this, we see that i∗i is not necessarily continuous at λ is zero. Also, note that at the point where
i∗i crosses zero (call this B) and the point where the right hand limit of i∗o at zero (call this A) satisfy
1
B = −
2(α + 1)
202
2α + 1
A = −
2(α + 1)
1 2α
= − −
2(α + 1) 2(α + 1)
2α
= B −
2(α + 1)
Since α is non-negative, this tells us that we should draw A below B in Figure 12.3.
12.10 Some MatLab Implementations:
We can implement the sgn or signum function in MatLab as follows:
Listing 12.1: Implementing The Signum Function

f u n c t i o n t = MySignum ( a r g )
%
% a r g i s a r e a l number and
5 % Mysignum ( a r g ) r e t u r n s 1 i f a r g i s > = 0 and − 1 e l s e .
%
n = length ( arg ) ;
t = zeros (1 , n ) ;
for i = 1 : n
10 t ( i ) = 1;
i f arg ( i ) < 0
t ( i ) = −1.0;
end
end
The unit step function u is listed below:
Listing 12.2: Implementing The Unit Step Function

f u n c t i o n t = MyStep ( a r g )
%
% a r g i s a r e a l number and
5 % MyStep ( a r g ) r e t u r n s 1 i f a r g i s > = 0 and 0 e l s e .
%
n = length ( arg ) ;
t = zeros (1 , n ) ;
for i = 1 : n
10 t ( i ) = 1;
i f arg ( i ) < 0
t ( i ) = 0.0;
203
end
end
We can then define the normalized inside current using these two files:
Listing 12.3: The Normalized Inner Current

f u n c t i o n t = I n S i d e C u r r e n t ( a l p h a , lambda )
%
% compute c u r r e n t i n s i d e t h e f i b e r
%
5 n = l e n g t h ( lambda ) ;
t = zeros (1 , n ) ;
for i =1: n
t ( i ) = ( exp ( − 1 . 0 ∗ abs ( lambda ( i ) ) ) ∗ MySignum ( lambda ( i ) ) . . .
− 2 . 0 ∗ MyStep ( lambda ( i ) ) ) / . . .
10 ( 2 . 0 ∗ ( alpha + 1 . 0 ) ) ;
end
You might wonder why we made the signum and unit step function so complicated looking. A
first try at the signum function, step function and inner current function might be
Listing 12.4: A Naive Step Function Implementation

f u n c t i o n t = MySignum ( a r g )
%
t = 1;
i f arg < 0
5 t = −1;
end
f u n c t i o n t = MyStep ( a r g )
%
10 t = 1.0;
i f arg < 0
t = 0.0;
end
15 I n s i d e C u r r e n t ( a l p h a , lambda )
%
t = ( exp ( − 1 . 0 ∗ abs ( lambda ) ) ∗ MySignum ( lambda ) − 2 . 0 ∗ MyStep ( lambda ) ) . . .
/ ( 2 . 0 ∗ ( alpha + 1 . 0 ) ) ;
This seems fine, but when we want to plot, we must use the lines
Listing 12.5: Plotting The Naive Step Function

>> lambda = l i n s p a c e ( − 6 , 6 , 2 0 0 ) ;
204
>> I 0 = I n S i d e C u r r e n t ( 0 . 5 , lambda ) ;
and you’ll see the plot is wrong. The reason is that when we send in a vector lambda into InSide-
Current, a vector is sent into the MyStep and MySignum functions. The conditional if arg is the
MySignum function does not behave the way we want it to in this case. What we want is that the
vector lambda is used in the inequality check to create a new vector t whose value t(i) is either 1 of
−1 depending on the value of lambda(i).
However what happens is that we perform the inequality check on each component of lambda and
keep resetting the value to t in the function to 1 or −1 as appropriate. Since the last value of lambda is
6, the value returned from MySignum is 1. A similar thing happens in MyStep and the value returned
from MyStep is always 1. Hence the inner current value is wrong and we must handle the conditional
differently. We do this by introducing the vector character of the space argument lambda directly.
Now the inner current plots are correct.
12.10.1 Runtime Results:
To use our functions to generate some plots is very easy. Here is a code fragment to do that:
Listing 12.6: Plotting Cable Currents

>> path ( path , ’/local/petersj/BioInfo/Cable’ ) ;
>> lambda = l i n s p a c e ( − 6 , 6 , 2 0 0 ) ;
5 >> I 2 = I n S i d e C u r r e n t ( 2 . 0 , lambda ) ;
>> I 4 = I n S i d e C u r r e n t ( 2 0 . 0 , lambda ) ;
%
% p l o t a l l g r a p h s on t h e same p l o t
10 %
>> p l o t ( lambda , I0 , ’r-’ , . . .
lambda , I1 , ’g-’ . . .
lambda , I2 , ’b-’ . . .
lambda , I3 , ’y-’ . . .
15 lambda , I4 , ’k-’ ) ;
We show the normalized inner current, i∗i versus lambda plots for a variety of α ration in Figure
( 12.4). After we generated the plot via the MatLab command, we use options in the pop-up graph for
the axis legends, titles and so forth to alter the appearance of the graph to our liking.
205
Figure 12.4: Inner Currents
12.10.2 Exercises:
1. Write Matlab functions to implement all the infinite cable transient variable solutions using as
many arguments to the functions as are needed.
(a) vm
(b) ii
(c) io
(d) vi
(e) vo
2. Generate a parametric plot of each of these variables versus the space variable z on a reasonable
size range of z for the parameters λc and Ie∗ .
(a) vm
(b) ii
(c) io
(d) vi
(e) vo
206
3. Write Matlab functions to implement all the remaining infinite cable normalized transient vari-
able solutions:
∗
(a) vm
(b) i∗o
(c) vi∗
(d) vo∗
4. Generate a parametric plot of each of these variables versus the space variable λ on a reasonable
size range of λ for the parameter α. This is what we did for the inner normalized current already.
∗
(a) vm
(b) i∗i
(c) i∗o
(d) vi∗
(e) vo∗
207
208
Chapter 13
The Finite and Half-Infinite Space Cable
We are actually interested in a model of information processing that includes a dendrite, a cell body
and an axon. Now we know that the cables that make up dendrites and axons are not infinite in extent.
So although we understand the currents and voltages change in our infinite cable model, we still need
to figure out how these solutions change when the cable in only finite in extent. A first step in this
direction is to consider a half-infinite cable such as shown in Figure 13.1 and then a finite length cable
like in Figure 13.2.
In both figures, we think of a real biological dendrite or axon as an inner cable surrounded by a
thin cylindrical sheath of seawater. So the outer resistance ro will be the resistance of seawater. At
first, we think of the cable as extending to the right forever; i.e. the soma is infinitely far from the
front end cap of the cable. This is of course not realistic, but we can use this thought experiment as
a vehicle towards understanding how to handle a finite cable attached to a soma. Before we had an
impulse current of magnitude I injected at some point on the outer cylinder and uniformly distributed
around the outer cylinder wall. Now we inject current directly into the front face of our cables. In
the finite length L cable case, there will also be a back end cap at z = L. This back endcap will
be attached to the soma. Then, although we could have the membrane properties of the cable endcap
and the soma itself be different, a reasonable assumption is to make them identical. Hence the back
endcap of the cable is a portion of the cell soma. At any rate, in both situations, the front endcap of
the cable is a logical place to think of current as being injected.
We will begin our modeling with a half-infinite cable. Once we know how to model the front
209
Figure 13.1: A Half-Infinite Dendrite or Axon Model
endcap current injection in this case, we will move directly to the finite cable model.
13.1 The Half-Infinite Cable Solution:
We inject an idealized pulse of current into the inner cable at z = 0 but instead inject into the front
face of the cable. Since the cable is of radius a, this means we are injected current into a membrane
cap of surface area π a2 . Note there is no external current source here and hence ke is zero. The
underlying cable equation is
d2 vm
λ2c − vm = 0, z ≥ 0
dz 2
with solution
z
vm (z) = A exp − ,z ≥ 0
λc
for some value of A which we will determine in a moment. We know that the membrane current
density is given by
210
km (z) = gm vm (z)
and further, the inner current satisfies
dii
= −km (z) = −gm vm (z)
dz
Since the cable starts at z = 0 and moves off to infinity, we will integrate this differential equation
from z to ∞ so that we can take advantage of the fact that the current at ∞ must be zero. We find
Z ∞ dii Z ∞
u
du = −gm A e− λc du
z dz z
z
ii (∞) − ii (z) = −gm λc Ae− λc
We conclude
z
ii (z) = gm λc Ae− λc
We also know that current of magnitude I is being injected into the front face of the inner cable; hence
ii (0) must be I. This tells us that
ii (0) = gm λc A = I
Combining, we have for positive z:
211
I z
vm (z) = e− λc
gm λc
z
ii (z) = I e− λc
From Ohm’s Law, we know that the ratio of current to voltage is conductance. The work above
ii (0)
suggests that we can define the conductance of the inner cable at z = 0 by the ratio vm (0)
. Therefore
the ratio of this current to voltage at z = 0, defines an idealized conductance for the end cap of the
cable. This conductance is called the Thevenin Equivalent Conductance of the half-infinite cable. It
is denoted by G∞ . The ratio is easy to compute
ii (0)
G∞ =
vm (0)
= gm λc
We can show that G∞ is dependent on the geometry of the cable; indeed, G∞ is proportional to a to
the three-halves power when ri is much bigger than ro . To see this, recall that the definition of λc
gives us that
s
gm
G∞ =
(ri + ro )
and so if ri is much bigger than ro , we find that
s
gm
G∞ ≈
ri
For a cylindrical cell of radius a, we know
212
ρi
ri =
πa2
gm = 2πaGm
and so
s
2Gm 3
G∞ ≈ π a2
ρi
which tells us that G∞ is proportional to the 3/2 power of a. Thus, larger fibers have larger character-
istic conductances!
If a cable is many space constants long (remember the space constant is proportional to the square
root of a, then the half-infinite model we discuss here may be appropriate. We will be able to show
this is a reasonable thing to do after we handle the true finite cable model. Once that is done, we will
see that the solutions there approach the half-infinite model solutions as L goes to infinity.
13.2 The Finite Cable Solution: Current Initialization:
If the cable becomes a piece of length L as shown in Figure 13.2, then there are now two faces to deal
with; the input face through which a current pulse of size I is delivered into some conductance and an
output face at z is L which has a output load conductance of Ge . Ge represents either the conductance
of the membrane that caps the cable or the conductance of another cable or cell soma attached at this
point.
We again have no external source and so the cable equation is
d2 vm
λ2c − vm (z) = 0, 0 ≤ z ≤ L
dz 2
The general solution to this homogeneous equation has been discussed before. The solution we seek
213
Figure 13.2: Finite Cable
will also need two boundary conditions to be fully specified. The general form of the membrane
potential solution is
z z
vm (z) = A1 e λc + A2 e− λc , 0 ≤ z ≤ L
We will rewrite this in terms of the new functions hyperbolic sine and hyperbolic cosine defined as
follows:
z z
z e λc + e− λc
cosh( ) =
λc 2
z z
z e − e− λc
λ c
cosh( ) =
λc 2
leading to the new form of the homogeneous solution
z z
vm (z) = A1 cosh( ) + A2 sinh( ), 0 ≤ z ≤ L
λc λc
214
It is convenient to reorganize this yet again and rewrite in another equivalent form as
L−z L−z
vm (z) = A1 cosh( ) + A2 sinh( ), 0 ≤ z ≤ L
λc λc
Now the membrane current density satisfies
km (z) = gm vm (z)
L−z L−z
= gm A1 cosh( ) + gm A2 sinh( )
λc λc
Further, since
d
cosh(z) = sinh(z)
dz
d
sinh(z) = cosh(z)
dz
we can use the internal current equation to find
dii
= −km (z)
dz
L−z L−z
= −gm A1 cosh( ) − gm A2 sinh( )
λc λc
Integrating, we find the possible inner current solution to be
L−z L−z
ii (z) = gm λc A1 sinh( ) + gm λc A2 cosh( )
λc λc
At z = 0, ii is I and since the conductance at z = L is Ge , the current at L must be
215
ii (L) = Ge vm (L)
Now
0 0
vm (L) = A1 cosh( ) + A2 sinh( )
λc λc
= A1
and
L L
ii (0) = gm λc A1 sinh( ) + gm λc A2 cosh( )
λc λc
0 0
ii (L) = gm λc A1 sinh( ) + gm λc A2 cosh( )
λc λc
= A2 gm λc
and so
L L
I = gm λc (A1 sinh( ) + A2 cosh( )
λc λc
A1 Ge = A2 gm λc
This implies using the definition of G∞
L L
I = G∞ (A1 sinh( ) + A2 cosh( )
λc λc
A1 Ge = A2 G∞
Thus,
216
L Ge L
I = A1 G∞ (sinh( ) + cosh( )
λc G∞ λc
giving us
I 1
A1 =
G∞ sinh( λc ) + GG∞e cosh( λLc )
L
IGe 1
A2 =
G∞ sinh( λc ) + GG∞e cosh( λLc )
2 L
This leads to the solution we are looking for
L−z Ge
I cosh( λc ) + G∞
sinh( L−z
λc
)
vm (z) = Ge
G∞ sinh( λLc ) + G∞
cosh( λLc )
L−z L−z
I G∞ sinh( λc ) + Ge cosh( λc )
ii (z) =
G∞ sinh( λLc ) + GG∞e cosh( λLc )
Note that at 0, we find
L Ge
I cosh( λc ) + G∞
sinh( λLc )
vm (0) = Ge
G∞ sinh( λLc ) + G∞
cosh( λLc )
ii (0)
From Ohm’s Law, the conductance we see at 0 is given by vm (0)
. We will call this the Thevenin Equiv-
alent Conductance looking into the cable of length L at 0 or simply the Thevenin Input Conductance
of the Finite Cable and denote it by the symbol GT (L) since its value clearly depends on L. It is given
by
Ge
sinh( λLc ) + G∞
cosh( λLc )
GT (L) = G∞ Ge
cosh( λLc ) + G∞
sinh( λLc )
217
The hyperbolic function tanh is defined by
sinh(u)
tanh(u) =
cosh(u)
and it is easy to show that as u goes to infinity, tanh(u) goes to 1. We can rewrite the formula for
GT (L) to be
Ge
G∞
+ tanh( λLc )
GT (L) = G∞ Ge
G∞
tanh( λLc ) + 1
and so as L goes to infinity, we find
Ge
G∞
+ 1
lim GT (L) = G∞ Ge
L→∞
G∞
+ 1
= G∞
Hence, the Thevenin input conductance of the cable approaches the idealized Thevenin input conduc-
tance of the half-infinite cable.
There are several interesting cases: for convenience of exposition, let’s define
L−z Ge
Z = , H = ,
λc G∞
L
L = , D = sinh(L) + H cosh(L)
λc
These symbols allow us to rewrite our solutions more compactly as
I cosh(Z) + H sinh(Z)
vm (z) =
G∞ sinh(L) + H cosh(L)
218
I cosh(Z) + H sinh(Z)
=
G∞ D
I G∞ sinh(Z) + Ge cosh(Z)
ii (z) =
I G∞ sinh(Z) + Ge cosh(Z)
=
G∞ D
sinh(L) + H cosh(L)
GT (L) = G∞
cosh(L) + H sinh(L)
Ge = 0 If the conductance of the end cap is zero, then H is zero and no current flows through the
endcap. We see
sinh(L)
GT (L) = G∞
cosh(L)
= G∞ tanh(L)
Ge = G∞ If the conductance of the end cap is G∞ , then H is one and we see the finite cable acts like
the half-infinite cable:
sinh(L) + cosh(L)
GT (L) = G∞
cosh(L) + sinh(L)
= G∞
Ge = ∞ If the conductance of the end cap is ∞, the end of the cable acts like it is short-circuited, H
is infinity. Divide our original conductance solution by H top and bottom and letting K denote
the reciprocal of H, we see:
K sinh(L) + cosh(L)
GT (L) = G∞
K cosh(L) + sinh(L)
Now K is zero here so we get
219
cosh(L)
GT (L) = G∞
sinh(L)
= G∞ coth(L)
13.2.1 Parametric Studies:
We can calculate that
vm (L) 1
=
vm (0) cosh( λc ) + GG∞e sinh( λLc )
L
L Ge
For convenience, let’s think of L as λc
and ρ as G∞
. Then the ratio of the voltage at the end of the
cable to the voltage at the beginning can be expressed as
vm (L) 1
=
vm (0) cosh(L) + ρ sinh(L)
This ratio measures the attenuation of the initial voltage as we move down the cable toward the end.
We can plot a series of these attenuations for a variety of values of ρ. In Figure 13.3, the highest
ρ value is associated with the bottom most plot and the lowest value is associated with the top plot.
Note as ρ increases, there is more conductivity through the end cap and the voltage drops faster. The
top plot is for ρ is zero which is the case of no current flow through the end cap.
We can also look how the Thevenin equivalent conductance varies with the value of ρ. We can
easily show that
GT (L)
GT∗ (L) =
G∞
tanh(L) + ρ
=
1 + ρ tanh(L)
220
Figure 13.3: Attenuation Increases with ρ
In Figure 13.4, we see that the ρ is one is the plot to which the other choices approach. When ρ is
above one, the input conductance ratio curve starts above the ρ is one curve; when ρ is below one, the
ratio curve approaches from below.
13.2.2 Some MatLab Implementations:
We want to compare the membrane voltages we see in the infinite cable case to the ones we see in
the finite cable case. Now in the infinite cable case, I current is deposited at z = 0 and the current
injection spreads out uniformly to both sides of 0 leading to the solution
r0 I λc −|z|
vm (z) = e λc
2
where the finite cable case is missing the division by 2 because in a sense, the current is not allowed
to spread backwards. Hence to compare solutions, we will inject 2 I into the infinite cable at 0 and I
into the finite cable.
Now at z = 0, the finite cable solution gives
221
Figure 13.4: Finite Cable Input Conductance Study
I cosh(L) + H sinh(L)
vm (0) =
I 1 + H tanh(L)
=
G∞ H + tanh(L)
In the examples below, we set G∞ , λc and r0 are one and set the cable length to 3. Hence, since for
L = 3, tanh(L) is very close to one, we have
1 + H
vm (0) ≈ I
H + 1
≈ I
So for these parameters, we should be able to compare the infinite and finite cable solutions nicely.
MatLab code to implement the infinite cable voltage solution is given below:
Listing 13.1: Computing The Infinite Cable Voltage

function t = IniniteMembraneVoltage ( Iehat , . . .
r0 , . . .
lambda c , . . .
222
z)
5 %
% c o m p u t e membrane v o l t a g e i n s i d e a f i n i t e fiber
%
P r e f i x = ( I e h a t ∗ r0 ∗ lambda c ) / 2 . 0 ;
t = P r e f i x ∗ exp ( −1.0∗ abs ( z ) / l a m b d a c ) ;
It is straightforward to modify the code above to handle the finite cable case:
Listing 13.2: Computing The Finite Cable Voltage

function t = FiniteMembraneVoltage ( Iehat , . . .
Ginfinity , . . .
Ge , . . .
L,...
5 lambda c , . . .
z)
%
% c o m p u t e membrane v o l t a g e i n s i d e a f i n i t e f i b e r
%
10 Prefix = Iehat / Ginfinity ;
FixedArg = L / lambda c ;
R a t i o = Ge / G i n f i n i t y ;
Denominator = sinh ( FixedArg )+ R a t i o ∗ cosh ( FixedArg ) ;
Arg = ( L−z ) / l a m b d a c ;
15 N u m e r a t o r = c o s h ( Arg ) + R a t i o ∗ s i n h ( Arg ) ;
t = ( I e h a t / G i n f i n i t y ) ∗ ( Numerator / Denominator ) ;
13.2.3 Run-Time Results:
We try out these new functions in the following MatLab session:
Listing 13.3: A Finite Membrane Voltage MatLab Session

>> path ( path , ’/local/petersj/BioInfo/Cable’ ) ;
>> Ge = 0 . 1 ;
>> I e h a t = 1 . 0 ;
>> G i n f i n i t y = 1 . 0 ;
5 >> L = 3 . 0 ;
>> l a m b d a c = 1 . 0 ;
>> r 0 = 1 . 0 ;
>> Z = l i n s p a c e ( 0 , L , 2 0 0 ) ;
%
10 % Find V o l t a g e f o r i n f i n i t e c a b l e f o r 2 ∗ I e h a t
>> V m i n f i n i t y = I n f i n i t e M e m b r a n e V o l t a g e ( 2 ∗ I e h a t , r0 , l a m b d a c , Z ) ;
% F i n d V o l t a g e f o r f i n i t e c a b l e f o r I e h a t , Ge = 0 . 1
>> V m0 = F i n i t e M e m b r a n e V o l t a g e ( I e h a t , G i n f i n i t y , Ge , L , l a m b d a c , Z ) ;
223
15 >> V m1 = F i n i t e M e m b r a n e V o l t a g e ( I e h a t , G i n f i n i t y , 0 . 5 , L , l a m b d a c , Z ) ;
>> V m2 = F i n i t e M e m b r a n e V o l t a g e ( I e h a t , G i n f i n i t y , 0 . 7 , L , l a m b d a c , Z ) ;
>> V m3 = F i n i t e M e m b r a n e V o l t a g e ( I e h a t , G i n f i n i t y , . 9 0 , L , l a m b d a c , Z ) ;
20 % F i n d V o l t a g e f o r f i n i t e c a b l e f o r I e h a t , Ge = 1 . 1
% P l o t I n f i n i t e c a b l e and f i n i t e c a b l e V o l t a g e s f o r I e h a t , Ge = 0 . 1
>> p l o t ( Z , V m i n f i n i t y , ’g-’ , Z , V m0 , ’r-’ ) ;
>> p l o t ( Z , V m i n f i n i t y , ’g-’ , Z , V m6 , ’r-’ ) ;
30 % F i n d V o l t a g e f o r f i n i t e c a b l e f o r I e h a t , Ge = 5 0 . 0
>> V m7 = F i n i t e M e m b r a n e V o l t a g e ( I e h a t , G i n f i n i t y , 5 0 . 0 , L , l a m b d a c , Z ) ;
% P l o t I n f i n i t e c a b l e and f i n i t e c a b l e V o l t a g e s f o r I e h a t , Ge = 5 0 . 0
>> p l o t ( Z , V m i n f i n i t y , ’g-’ , Z , V m7 , ’r-.’ ) ;
40 % P l o t I n f i n i t e c a b l e and f i n i t e c a b l e V o l t a g e s f o r I e h a t , Ge = 0 . 0
We are choosing to look at these solutions for a cable length of 3 with all the other parameters set
to 1 for convenience except for the cable length which will be 3 and the endcap load conductance Ge
which we will vary. We are also injecting 2 Ie∗ into the infinite cable as we mentioned we would do.
Note the finite cable response attenuated more quickly than the infinite cable unless Ge is G∞ ! You
can see a variety of results in Figures 13.5(a) - 13.5(b).
13.2.4 Exercises:
1. Write Matlab functions to implement the finite cable transient variable solutions using as many
arguments to the functions as are needed.
(a) vm
(b) ii
224
(a) End Cap Load is 0.1 (b) End Cap Load is 1.0
Figure 13.5: Low End Cap Loads
(a) End Cap Load is 5.0 (b) End Cap Load is 50.0
Figure 13.6: High End Cap Loads
225
2. Generate a parametric plot of each of these variables versus the space variable z on a reasonable
size range of z for the parameters λc , Ie∗ , cable length L and Ge . The ratio of Ge to G∞ is a very
reasonable parameter to use.
(a) vm
(b) ii
3. Plot GT (L) versus L and the horizontal line G∞ on the same plot and discuss what is happening.
13.3 The Finite Cable: Voltage Initialization:
We can redo what we have discussed in the above using a different initial condition. Instead of
specifying initial current, we will specify initial voltage. As you might expect, this will generate
slightly different solutions. We use the same start:
L−z L−z
vm (z) = A1 cosh( ) + A2 sinh( )
λc λc
L−z L−z
ii (z) = A1 G∞ sinh( ) + A2 G∞ cosh( )
λc λc
Our boundary conditions are now vm (0) = V0 and ii (L) = Ge vm (L). Also, we will use the
abbreviations from before: H, Z and L but change D to
E = cosh(L) + H sinh(L)
B
Now let VL denote vm (L). Then it follows that A1 = VL . If we set BL = VL
, then
L−z L−z

vm (z) = VL cosh(
) + BL sinh( )
λc λc
L−z L−z

ii (z) = VL G∞ sinh( ) + BL cosh( )
λc λc
226
We know that ii (L) = Ge VL and so
0 0
ii (L) = VL G∞ (sinh( ) + BL cosh( ))
λc λc
Ge VL = VL BL G∞
The above implies BL = H. Finally, note that
L L
vm (0) = VL (cosh( ) + H sinh( ))
λc λc
= VL (sinh(L) + H cosh(L))
= VL E
V0
Hence, E
= VL and from this we obtain our final expression for the solution:
V0
vm (z) = (cosh(Z) + H sinh(Z))
E
V0
ii (z) = G∞ (sinh(Z) + H cosh(Z))
E
We will find that the Thevenin equivalent conductance at the end cap is still the same. We have the
same calculation as before
ii (0)
GT (L) =
vm (0)
sinh(L) + H cosh(L)
= G∞
cosh(L) + H sinh(L)
Finally, it is easy to see that the relationship between the current and voltage initialization condition
is given by
227
V0 GT (L) = ii (0)
We can then find voltage and current equations for various interesting end cap conductance loads:
Ge = 0: If the conductance of the end cap is zero, then H is zero and no current flows through the
endcap. We see
cosh(Z)
vm (z) = V0
cosh(L)
sinh(Z)
ii (z) = V0 G∞
cosh(L
GT (L) = G∞ tanh(L)
Ge = G∞ : If the conductance of the end cap is G∞ , then H is one and we see the finite cable acts
like the half-infinite cable:
cosh(Z) + sinh(Z)
vm (z) = V0
cosh(L) + sinh(L)
−z
= V0 exp( )
λc
sinh(Z) + cosh(Z)
ii (z) = V0 G∞
cosh(L) + sinh(L)
−z
= V0 G∞ exp( )
λc
Ge = ∞: If the conductance of the end cap is ∞, the end of the cable acts like it is short-circuited,
H is infinity. We see
228
sinh(Z)
vm (z) = V0
sinh(L)
cosh(Z)
ii (z) = V0 G∞
sinh(L
GT (L) = G∞ coth(L)
13.3.1 Exercises:
1. Write Matlab functions to implement vm , ii and GT (L) using as many arguments to the functions
as are needed. The arguments will be L, λc , z, V0 , G∞ and Ge
2. Using V0 = 1, λc = 5, L = 10, and G∞ = 2.0 and generate a parametric plot of each of these
variables versus the space variable z on [0, 10] for a reasonable size range of Ge . Discuss how
the special conductance cases above fit into these plots.
3. Assume L = 1 and λc = 1 also. Suppose sufficient current is injected to give V0 = 10 mV.

Let G∞ = 2.0.
(a) Let Ge = 0.5
i. Compute vm at z = 0.6 and 1.0. Compute vm for the infinite cable model too at these
points.
(b) Let Ge = 2.0
points.
(c) Let Ge = 50.0
points.
(d) Discus the results.
229
Figure 13.7: Dendrite Model With Synaptic Current Injections
13.4 Synaptic Currents:
We can have two types of current injection. The first is injected through the outer membrane and is
modeled by the pulses ke . We know the outer cylinder is a theoretical abstraction and so there is really
no such physical membrane. The second is injected into the front face of the cable in either a finite or
half-infinite case. This current is modeled as an initialization of the inner current ii . So consider the
model we see in Figure 13.7
The differential equation we would solve here would be
d2 vm
λ2c − vm = −ro λ2c I0 δ(z − z0 ) − ro λ2c I1 δ(z − z1 ) 0 ≤ z ≤ L
dz 2
ii (0) = I
ii (L) = Ge vm (L) (13.1)
Here current I is injected into the front face and two impulse currents are injected into the outer
cylinder. If we are thinking of this as a model of an axon, we could throw away the external sources
and think of the current I injected into the front face as the current that arises from membrane voltage
changes that propagate forward from the dendrite and soma system. Hence, the front face current I is
230
a lumped sum approximation of the entire dendrite and soma subsystem response.
On the other hand, if we are modeling a dendrite, we could think of the front face current I as a
lumped sum model of the synaptic voltages that have propagated forward up to that point from the
the rest of the dendrite system we are not modeling. The external current sources are then currents
induced by synaptic interactions or currents flowing through pores in the membrane. Of course,
voltage modulated gates would be handled differently!
Since our differential equation system is linear, to solve a problem like (13.1), we can simply add
together the solutions to individual problems. This is called superposition of solutions and it is a very
important tool in our work. Hence, to solve (13.1) we solve
d2 vm
λ2c − vm = 0, 0 ≤ z ≤ L
dz 2
ii (0) = I
ii (L) = Ge vm (L) (13.2)
and
d2 vm
λ2c − vm = −ro λ2c I0 δ(z − z0 ) 0 ≤ z ≤ L
dz 2
ii (0) = 0
ii (L) = Ge vm (L) (13.3)
and
d2 vm
λ2c − vm = −ro λ2c I1 δ(z − z1 ) 0 ≤ z ≤ L
dz 2
ii (0) = 0
ii (L) = Ge vm (L) (13.4)
231
and add the solutions together. Since we already know the solution to (13.2), it suffices to solve (13.3).
13.4.1 A Single Impulse:
Consider a family of problems of the form (13.5)
d2 vm
λ2c − vm = −ro λ2c I0 ken (z − z0 ) 0 ≤ z ≤ L
dz 2
ii (0) = 0
ii (L) = Ge vm (L) (13.5)
where the family {ken } of impulses are modeled as before: each is zero off [z0 − λc wn , z0 − λc wn ],
symmetric around z0 and the area under the curve is I0 for all n. We assume for now that the site of
current injection is z0 which is in (0, L). The case of z0 being 0 or L will then require only a slight
modification of our arguments which we will only sketch leaving the details to the reader. As usual,
each current pulse delivers I0 amps of current even though the base of the pulse is growing smaller and
smaller. Physically, we expect, like in the infinite cable problem, that the voltage acts like a decaying
exponential on either side of z0 . To see this is indeed the idealized solution we obtain when we let n
go to infinity, we resort to the following model:

z−z
n λc 0
A e , 0 ≤ z ≤ z0 − λc wn


1




 z−z z−z
n 0 − λ 0
vm (z) = C n e λc + D n e c + φnp (z), z0 − λc wn ≤ z ≤ z0 + λc wn


 z−z
− λ 0

 An
2e
c , z0 + λc wn ≤ z ≤ L


The parts of the model before z0 − λc wn and after z0 + λc wn are modeled with exponential decay,
while the part where the pulse is active is modeled with the full general solution to the problem having
the form φh (z) + φnp (z), where φh is the homogeneous solution to the problem and φnp is the particular
solution obtained from the variations of parameters technique for a pulse ken . Since the pulse ken is
smooth, we expect the voltage solution to be smooth also; hence our solution and its derivative must
232
be continuous at the points z0 − λc wn and z0 + λc wn . This will give us four equations in four
unknowns we can solve for the constants An1 , An2 , C n and Dn .
Recall the auxiliary equation for this differential equation is
λ2c r2 − 1 = 0
1
with roots λc
and − λ1c . The homogeneous solution is then
z−z0 z−z0
φh (z) = B1 e λc + B2 e− λc
Using the method of Variation of Parameters, we search for a particular solution of the form
z−z0 z−z0
φnp (z) = U1 (z)e λc + U2 (z)e− λc
where the coefficient functions U1 and U2 satisfy
     
z−z0 z−z0
− dU1
 e λc e λc
  dz   0 
    =  
z−z0 z−z0
− λ1c e−
     
1 dU2
λc
e λc λc
dz
−ro ken
This is easily solved using Cramer’s rule to give
dU1 ro λc − z−z 0
= − k e e λc
dz 2
dU2 ro λc z−z0
= k e e λc
dz 2
We can integrate then to obtain
233
r 0 λc Z z n x−z0
U1 (z) = − ke (x − z0 ) e− λc dx
2 z0
r0 λc Z z n x−z0
U2 (z) = ke (x − z0 ) e λc dx
2 z0
giving
z−z0 z−z0
φnp (z) = U1 (z) e λc + U2 (z) e− λc
! !
r0 λc Z z x−z0 z−z0 r 0 λc Z z u z−z0
= − ke (x − z0 ) e− λc dx e λc + ke (x − z0 ) e λc dx e− λc
2 z0 2 z0
Z z Z z
r0 λc x−z r 0 λc x−z
= − ke (x − z0 ) e λc dx + ke (x − z0 ) e− λc dx
2 z0 2 z0
Z z
z−x
= −r0 λc ke (x − z0 ) sinh( ) dx
z0 λc
Hence, the particular solution for pulse ken is
Z z z−x
φnp (z) = −r0 λc ke (x − z0 ) sinh( ) dx
z0 λc
13.4.2 Forcing Continuity in the Model:
Note that

z−z0
An
e λc , 0 ≤ z ≤ z0 − λc wn

 1


 λc
n
dvm

 z−z0 z−z0
Cn Dn − dφn
= e − λc e λc + p
, z0 − λc wn ≤ z ≤ z0 + λc wn
dz 


λc λc dz
n z−z0
 − A2 e− λc ,

z0 + λc wn ≤ z ≤ L


λ c
Now continuity at z0 − λc wn and z0 + λc wn gives
234
An1 e−wn = Cn e−wn + Dn ewn + φnp (z0 − λc wn )
An2 e−wn = Cn ewn + Dn e−wn + φnp (z0 + λc wn )

An1 −wn Cn −wn Dn wn dφn
e = e − e + p (z0 − λc wn )
λc λc λc dz
A n
Cn wn Dn −wn dφn
− 2 e−wn = e − e + p (z0 + λc wn )
λc λc λc dz
which can be rewritten in the form
An1 e−wn − : Cn e−wn − Dn ewn = φnp (z0 − λc wn ) (13.6)
An2 e−wn − Cn ewn − Dn e−wn = φnp (z0 + λc wn ) (13.7)

dφnp
An1 e−wn − Cn e−wn + Dn ewn = λc (z0 − λc wn ) (13.8)
dz
dφn
−An2 e−wn − Cn ewn + Dn e−wn = λc p (z0 + λc wn ) (13.9)
dz
Computing (Equation 13.7 + Equation 13.8), (Equation 13.7 - Equation 13.8), (Equation 13.9 and
Equation 13.9) and (Equation 13.9 - Equation 13.9), we find
dφnp
2An1 e−wn − 2Cn e−wn = φnp (z0 − λc wn ) + λc (z0 − λc wn )
dz
dφnp
−2Dn ewn n
= φp (z0 − λc wn ) − λc (z0 − λc wn )
dz
dφn
−2Cn ewn = φnp (z0 + λc wn ) + λc p (z0 + λc wn )
dz
n
dφ
2An2 e−wn − 2Dn e−wn = φnp (z0 + λc wn ) − λc p (z0 + λc wn )
dz
Although a bit messy, this can easily be solved to give
235
dφnp
2An1 e−wn = 2Cn e−wn + φnp (z0 − λc wn ) + λc (z0 − λc wn )
dz
dφnp dφn
= −(φnp (z0 + λc wn ) + λc (z0 + λc wn ))e−2wn + φnp (z0 − λc wn ) + λc p (z0 − λc wn )
dz dz
n
dφ
2An2 e−wn = 2Dn e−wn + φnp (z0 + λc wn ) − λc p (z0 + λc wn )
dz
n
dφ p dφn
= −(φnp (z0 − λc wn ) − λc (z0 + λc wn ))e−2wn + φnp (z0 + λc wn ) − λc p (z0 + λc wn )
dz dz
or
1 n dφnp −wn 1 n dφnp

An1 = − (φp (z0 + λc wn ) + λc (z0 + λc wn ))e + (φp (z0 − λc wn ) + λc (z0 − λc wn ))ewn
2 dz 2 dz
1 n dφnp 1 dφ n
An2 = − (φp (z0 − λc wn ) − λc (z0 + λc wn ))e−wn + (φnp (z0 + λc wn ) − λc p (z0 + λc wn ))ewn
2 dz 2 dz
13.4.3 The Limiting Solution:
The above solutions work for all n. We note that it is straightforward to show we must have
Z z0 +λc wn z0 + λc wn − x
φnp (z0 + λc wn ) = −r0 λc ken (x − z0 ) sinh( )
z0 λc
and so
I0
lim φnp (z0 + λc wn ) = −r0 λc sinh(0)
n→∞ 2
= 0
In a similar fashion, we can show
236
I0
lim φnp (z0 − λc wn ) = r0 λc sinh(0)
n→∞ 2
= 0
Finally, since
dφnp n
Z z
z−x
(z) = −r0 λc ke (z − z0 )sinh(0) − r0 ken (x − z0 )cosh( )dx
dz z0 λc
we see
dφnp Z z0 +λc wn
z−x
(z0 + λ − cwn ) = −r0 ken (x − z0 )cosh( )dx
dz z0 λc
which gives
dφnp I0
lim (z0 + λc wn ) = −r0 λc cosh(0)
n→∞ dz 2
I0
= −r0 λc
2
and similarly
dφnp I0
lim (z0 − λc wn ) = r0 λc cosh(0)
n→∞ dz 2
I0
= r 0 λc
2
Thus in the limit, we obtain the limiting constants
237
A1 = lim An1
n→∞
r0 λc I0
=
2
A2 = lim An2
n→∞
r0 λc I0
=
2
This gives the limiting solution

z−z0
r0 λc I0
e , 0 ≤ z ≤ z0


 λc
2
vm (z) = z−z
r0 λc I0 − λ 0
e , z0 ≤ z ≤ L

c


2
which is essentially our usual idealized impulse solution from the infinite cable model
r0 λc I0 − |z−z 0|
vm (z) = e λc , 0 ≤ z ≤ L
2
Note the values of Cn and Dn are not important for the limiting solution.
13.4.4 Satisfying the Boundary Conditions:
Since
dii
= −gm vm
dz
we see that for z below z0 − λc wn , we have
238
z−z0
ii (z) = −gm λc An1 e λc + Bn
z−z0
= −G∞ An1 e λc + Bn
and the boundary condition ii (0) = 0 then implies
z0
Bn = G∞ An1 e− λc
and for the second boundary condition, ii (L) = Ge vm (L), we use the last part of the definition of vm
to give us
z−z0
ii (z) = G∞ An2 e− λc + En
and
L−z0 L−z0
G∞ An2 e− λc + E n = Ge An2 e− λc
or
L−z0
En = An2 e− λc (Ge − G∞ )
Hence, from the above, we see that the limiting inner current solutions satisfy
B = lim Bn
n→∞
239
r0 λc I0 − λz0
= G∞ e c
2
E = lim En
n→∞
r0 λc I0 − L−z 0
= Ge e λc
2
giving for z below z0
r0 λc I0 z−z 0 r0 λc I0 − λz0
ii (z) = −G∞ e λc + G∞ e c
2 2
and for z above z0 ,
r0 λc I0 − z−z 0 r0 λc I0 − L−z 0
ii (z) = G∞ e λc + Ge e λc
2 2
13.4.5 Some Results:
We can now see the membrane voltage solutions for the stated problem
d2 vm
λ2c − vm = 0, 0 ≤ z ≤ L
dz 2
ii (0) = I
ii (L) = Ge vm (L)
in Figure 13.8. Note here there are no impulses applied. If we add the two impulses at z0 and
z1 as described by the differential Equations (13.3) and (13.1), the solution to the full problem for
somewhat weak impulses at two points on the cable can be seen in Figure 13.9. For another choice
of impulse strengths, we see the summed solution in Figure 13.10. For ease of comparison, we can
plot the solutions for no impulses, two impulse of low strength and two impulses of higher strength
240
Figure 13.8: Finite Cable Initial Endcap Current
simultaneously in Figure 13.11
13.5 Implications:
Even though we have still not looked into the case of time dependent solutions, we can still say a lot
about the nature of the solutions we see in the time independent case.
• The space constant λc tells us how far we must be from the site of input current to see significant
attenuation of the resulting potential. Thus, if λc << 1, the cable’s membrane potential is close
to position independent.
• An electrode used to input current or measure voltage can b e thought of as infinitesimal in tip
size if the tip size is very small compared to λc .
• Our underlying cable equation is a linear PDE. Hence, the superposition principle applies and
we can use it to handle arbitrary arrangements of current sources.
241
Figure 13.9: Finite Cable Current Initializations: Strong Impulses
Figure 13.10: Finite Cable Current Initializations: Strong Impulses
242
Figure 13.11: Three Finite Cable Current Initializations
• We already know that
s
a
λc ≈
2ρi Gm
s
1 √
≈ a
2ρ)iGm
implying λc decreases as the cable fiber inner radius decreases.
µF
Now let as usual a be cable radius in µm, Cm be membrane capacitance in cm2
, Gm be membrane
mS MΩ
conductance in cm2
, ri be internal resistance of the protoplasm per unit length in cm
, λc be the cable
space constant in mm and τm be the cable membrane time constant in msec. Then consider a table of
these typical cable constants as shown in Table 13.1.
1000λc µm 4000
From Table 13.1, we see that the earthworm give aµm
is 52.5
or 76.2. If we assume this ratio
holds, then for a cable with a equal to 0.5 µm, we see that the space constant for this cable would
be 76.2 × 0.5 µm or 38.1 µm which is 0.38 mm. The earthworm cable fiber is unmylenated and so
signals are not insulated from transmission loss. This extrapolation shows that in this unmylenated
243
Species a Cm Gm ri λc τm
Squid (Loligo Peali) 250 1 1 0.015 6.5 1
Lobster (Homanus Vulgaris) 37.5 1 0.5 1.4 2.5 2
Crab (Carcinus Maenas) 15 1 0.14 13.0 2.3 7
Lobster (Homanus Americanus) 50 - 0.13 1.0 5.1 -
Earthworm (Lumbricus Terrestris) 52.5 0.3 0.083 2.3 4.0 3.6
Marine Worm (Myxicula Infundibulum) 280 0.75 0.012 0.023 5.4 0.9
Cat Motoneuron - 2 0.4 - - 5.0
Frog Muscle Fiber (Sartorius) 37.5 2.5-6.0 0.25 4.5 2.0 10.0-24.0
Table 13.1: Typical Cable Constants
case, we would expect the fiber to transmit signal poorly as the fiber radius drops. Of course, many
species protect themselves against this transmission loss by shielding the fibers using mylenin, but
that is another story.
244
Chapter 14
Simplified Dendrite - Soma - Axon

Information Processing
Let’s review the basics of information processing in a typical neuron. As we have mentioned before,
there are many first sources for this material; some of them are Introduction to Neurobiology (Hall
(5) 1992) , Ionic Channels of Excitable Membranes (Hille (6) 1992) , Foundations of Cellular
Neurophysiology (Johnston and Wu (8) 1995) ], Rall’s review of cable theory in the 1977 Hand-
book of Physiology (Rall (10) 1977) and Weiss’s Cellular Biophysics: Transport and Electrical
Properties (Weiss (12) 1996) and (Weiss (13) 1996) .
Our basic model consists of the following structural elements: A neuron which consists of a
dendritic tree (which collects sensory stimuli and sums this information in a temporally and spatially
dependent way), a cell body (called the soma) and an output fiber (called the axon). Individual
dendrites of the dendritic tree and the axon are all modeled as cylinders of some radius a whose
length ` is very long compared to this radius and whose walls are made of a bilipid membrane. The
inside of each cylinder consists of an intracellular fluid and we think of the cylinder as lying in a bath
of extracellular fluid. So for many practical reasons, we can model a dendritic or axonal fiber as two
concentric cylinders; an inner one of radius a (this is the actual dendrite or axon) and an outer one
with the extracellular fluid contained in the space between the inner and outer membranes.
The potential difference across the inner membrane is essentially due to a balance between the
electromotive force generated by charge imbalance, the driving force generated by charge concen-
245
tration differences in various ions and osmotic pressures that arise from concentration differences in
water molecules on either side of the membrane. Roughly speaking, the ions of importance in our
simplified model are the potassium K + , sodium N a+ and chloride Cl− ions. The equilibrium po-
tential across the inner membrane is about −70 millivolts and when the membrane potential is driven
above this rest value, we say the membrane is depolarized and when it is driven below the rest po-
tential, we say the membrane is hyperpolarized. The axon of one neuron interacts with the dendrite
of another neuron via a site called a synapse. The synapse is physically separated into two parts: the
presynaptic side (the side the axon is on) and the postsynaptic side (the side the dendrite is on). There
is an actual physical gap, the synaptic cleft, between the two parts of the synapse. This cleft is filled
with extracellular fluid.
If there is a rapid depolarization of the presynaptic site, a chain of events is initialized which
culminates in the release of specialized molecules called neurotransmitters into the synaptic cleft.
There are pores embedded in the postsynaptic membrane whose opening and closing are dependent
on the potential across the membrane that are called voltage-dependent gates. In addition, the gates
generally allow the passage of a specific ion; so for example, there are sodium, potassium and chloride
gates. The released neurotransmitters bind with the sites specific for the N a+ ion. Such sites are called
receptors. Once bound, N a+ ions begin to flow across the membrane into the fiber at a greater rate
than before. This influx of positive ions begins to drive the membrane potential above the rest value;
that is, the membrane begins to depolarize. The flow of ions across the membrane is measured in gross
terms by what are called conductances. Conductance has the units of reciprocal ohms; hence, high
conductance implies high current flow per unit voltage. Thus the conductance of a gate is a good way
to measure its flow. We can say that as the membrane begins to depolarize, the sodium conductance,
gN a , begins to increase. This further depolarizes the membrane. However, the depolarization is self-
limited as the depolarization of the membrane also triggers the activation of voltage-dependent gates
for the potassium ion, K + , which allow potassium ions to flow through the membrane out of the cell.
So the increase in the sodium conductance, gN a triggers a delayed increase in potassium conductance,
gK (there are also conductance effects due to chloride ions which we will not mention here). The net
effect of these opposite driving forces is the generation of a potential pulse that is fairly localized in
both time and space. It is generated at the site of the synaptic contact and then begins to propagate
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down the dendritic fiber toward the soma. As it propagates, it attenuates in both time and space. We
call these voltage pulses Post Synaptic Pulses or PSPs.
We model the soma itself as a small isopotential sphere, small in surface area compared to the
surface area of the dendritic system. The possibly attenuated values of the PSPs generated in the den-
dritic system at various times and places are assumed to propagate without change from any point on
the soma body to the initial segment of the axon which is called the axon hillock. This is a specialized
piece of membrane which generates a large output voltage pulse in the axon by a coordinated rapid
increase in gN a and gK once the axon hillock membrane depolarizes above a critical trigger value.
The axon itself is constructed in such a way that this output pulse, called the action potential, travels
without change throughout the entire axonal fiber. Hence, the initial depolarizing voltage impulse that
arrives at a given presynaptic site is due to the action potential generated in the presynaptic neuron by
its own dendritic system.
The salient features of our model are thus:
• Axonal and dendritic fibers are modeled as two concentric membrane cylinders.
• The axon carries action potentials which propagate without change along the fiber once they are
generated. Thus if an axon makes 100 synaptic contacts, we assume that the depolarizations of
each presynaptic membrane are the same.
• Each synaptic contact on the dendritic tree generates a time and space localized depolarization
of the postsynaptic membrane which is attenuated in space as the pulse travels along the fiber
from the injection site and which decrease in magnitude the longer the time is since the pulse
was generated.
• The effect of a synaptic contact is very dependent on the position along the dendritic fiber that
the contact is made–in particular, how far was the contact from the axon hillock (i.e., in our
model, how far from the soma?)? Contacts made in essentially the same space locality have a
high probability of reinforcing each other and thereby possibly generating a depolarization high
enough to trigger an action potential.
247
Figure 14.1: The Dendrite Fiber Model
• The effect of a synaptic contact is very dependent on the time at which the contact is made. Con-
tacts made in essentially the same time frame have a high probability of reinforcing each other
and thereby possibly generating a depolarization high enough to trigger an action potential.
14.1 A Simple Model of a Dendrite: The Core Conductor Model:
We can model the above dendrite fiber reasonably accurately by using what is called the core conduc-
tor model (see Figure 14.1).
We assume the following:
• The dendrite is made up of two concentric cylinders. Both cylinders are bilayer lipid mem-
branes with the same electrical characteristics. There is conducting fluid between both the inner
and outer cylinder (extracellular solution) and inside the inner cylinder (intracellular solution).
These solutions are assumed homogeneous and isotropic; in addition, Ohm’s law is valid within
them.
248
• All electrical variables are assumed to have cylindrical symmetry; hence, all variables are in-
dependent of the traditional polar angle θ. In particular, currents in the inner and outer fluids
are longitudinal only (that is, up and down the dendritic fiber). Finally, current through the
membrane is always normal to the membrane (that is the membrane current is only radial).
• A circuit theory description of currents and voltages is adequate for our model. At a given
position along the cylinder, the inner and outer conductors are at the same potential (if you slice
the cylinder at some point along its length perpendicular to its length, all voltage measurements
in the inner and outer solutions will have the same voltage). The only radial voltage variation
occurs in the membrane itself.
There are many variables associated with this model; although the model is very simplified from
the actual biological complexity, it is still formidably detailed. These variables are described below:
z: the position of along the cable measured from some reference zero (m),
t: the current time (sec),
Io (z, t): the total longitudinal current flowing in the +z direction in the outer conductor (amps),
Ii (z, t): the total longitudinal current flowing in the +z direction in the inner conductor (amps),
Jm (z, t): the membrane current density in the inner conductor to the outer conductor (amp/m2 ),
Km (z, t): the membrane current per unit length from the inner conductor to the outer conductor
(amp/m),
Ke (z, t): the current per unit length due to external sources applied in a cylindrically symmetric
manner. So it we think of a presynaptic neuron’s axon generating a postsynaptic pulse in a
given postsynaptic neuron, we can envision this synaptic contact occurring at some point z
along the cable and the resulting postsynaptic pulse as a Dirac delta function impulse applied
to the cable as a high current Ke which lasts for a very short time (amp/m),
Vm (z, t): the membrane potential which is consider + when the inner membrane is positive with
respect to the outer one (volts),
249
Vi (z, t): the potential in the inner conductor (volts),
Vo (z, t): the potential in the outer conductor (volts),
ro : the resistance per unit length in the outer conductor (ohms/m),
ri : the resistance per unit length in the inner conductor (ohms/m),
a: the radius of the inner cylinder (m).
Careful reasoning using Ohm’s law and Kirchhoff’s laws for current and voltage balance lead to the
well-known steady state equations:
∂Ii ∂Io
= −Km (z, t), = Km (z, t) − Ke (z, t) (14.1)
∂z ∂z
∂Vi ∂Vo
= −ri Ii (z, t), = −ro Io (z, t), Vm = Vi − Vo (14.2)
∂z ∂z
These equations look at what is happening in the concentric cylinder model at equilibrium; hence, the
change in the potential across the inner membrane is due entirely to the longitudinal variable z. From
equation 14.2, we see
∂Vm ∂Vi ∂Vo

= − = ro Io (z, t) − ri Ii (z, t)
∂z ∂z ∂z
implying
∂ 2 Vm ∂Io ∂Ii
2
= ro − ri = (ri + ro )Km (z, t) − ro Ke (z, t).
∂z ∂z ∂z
Using equation 14.2, we then obtain the core conductor equation
∂ 2 Vm
= (ri + ro )Km (z, t) − ro Ke (z, t). (14.3)
∂z 2
250
It is much more useful to look at this model in terms of transient variables which are perturbations
from rest values. We define
Vm (z, t) = Vm0 + vm (z, t), Km (z, t) = Km

0
+ km (z, t), Ke (z, t) = Ke0 + ke (z, t) (14.4)
where the rest values are respectively Vm0 (membrane rest voltage), Km
0
(membrane current per length
base value) and Ke0 (injected current per length base value). With the introduction of these transient
variables, we are able to model the flow of current across the inner membrane more precisely. We
introduce the conductance per length gm ( Siemens/cm or 1/(ohms cm) and capacitance per length cm
(fahrads/cm) of the membrane and note that we can think of a patch of membrane as as simple RC
circuit. This leads to the transient cable equation
∂ 2 vm ∂vm
2
= (ri + ro )gm vm (z, t) + (ri + ro )cm − ro ke (z, t). (14.5)
∂z ∂t
If we write the transient cable equation into an appropriate scaled form, we gain great insight into how
membrane voltages propagate in time and space relative to what may be called fundamental scales.
Define
cm
τM = (14.6)
gm
1
λc = q (14.7)
(ri + ro ) gm
Note that τM is independent of the geometry of the cable and depends only on dendritic fiber charac-
teristics. We will call τM the fundamental time constant (that is, this constant determines how quickly
a membrane potential decays to one half on its initial value) of the solution for reasons we will see
shortly. On the other hand, the constant λc is dependent on the geometry of the cable fiber and we
will find it is the fundamental space constant of the system that is, the membrane potential decays to
251
one half of its value within this distance along the cable fiber).
If we let CM and GM denote the capacitance and conductance per square cm of the membrane,
the circumference of the cable is 2πa and hence the capacitance and conductance per length are given
by
cm = 2πaCM (14.8)
gm = 2πaGM (14.9)
CM
and we see clearly that the ratio τM is simply GM
. This clearly has no dependence on the cable radius
showing yet again that this constant is geometry independent. We note that the units of τM are in
seconds. The space constant can be shown to have units of cm and defining ρi to be the resistivity
(ohm-cm) of the inner conductor, we can show that
ρi
ri = . (14.10)
π a2
From this it follows that
1 1
λC = √ a2 . (14.11)
2ρi GM
Clearly, the space constant is proportional to the square root of the fiber radius and the proportionality
constant is geometry independent. Another important constant is the Thévenin equivalent conduc-
tance, G∞ , which is defined to be
s
gm
G∞ = λC gm = . (14.12)
ri + ro
For most biologically plausible situations, the outer conductor resistance per unit length is very small
252
in comparison to the inner conductor’s resistance per unit length. Hence, ri ro and equation 14.12
can be rewritten using equations 14.9 and 14.10 to have the form
s s
gm 2GM 3
G∞ = = π a2 . (14.13)
ri ρi
which shows that G∞ is proportional to the three halves power of the fiber radius a with a proportion-
1
ality constant which is geometry independent. With all this said, we note that ri + ro = λ2C gm
and
hence, we can rewrite the transient cable equation as
∂ 2 vm ∂vm
λ2C = v m + τ M − ro λ2C ke . (14.14)
∂z 2 ∂t
14.2 Solutions to the Cable Model:
There are three important classes of solution to the properly scaled cable equation: for the cases of
an infinite, semi-infinite and finite length cable respectively; further, we are interested in both time
independent and dependent solutions. Since these kinds of solution will be useful in understanding
why we choose to augment our feed forward models of computation in the way that we do, we need
to discuss some of these details. We will avoid the derivations of these solutions as there are a number
of places where you can find such information, e.g. Rall, (Rall (10) 1977) (though it is NOT an easy
journey). Instead, let’s build a table which lists the salient characteristics of these solutions.
14.2.1 Time Independent Solutions:
The three types of solution here are for the infinite, semi-infinite and finite cable models. We model
the applied current as a current impulse of the form ke Ie δ(z − 0), where Ie is the magnitude of the
impulse which is applied at position z = 0 using the Dirac delta function δ(z − 0). The resulting
steady state equation is given by
253
d2 vm
λ2C = vm − ro λ2C Ie δ(z − 0).
dz 2
which has solution
λC ro Ie −|z|
vm (z) = e λC (14.15)
2
The noticeable characteristics of this solution are that its spatial decay is completely determined by
the space constant λC and the decay is symmetric across the injection site at z = 0. Within one space
constant, the potential drops by 1e .
In the semi-infinite cable case, we assume the cable begins at z = 0 and extends out to infinity to
the right. We assume a current Ie is applied at z = 0 and we can show the appropriate differential
equation to solve is
d2 vm
λ2C = vm , ii (0) = Ie
dz 2
where ii denotes the transient inner conductor current. This system has solution
Ie − z
vm (z) = e λC
gm λC
s
ri + ro − z
= Ie e λC
gm
ii (0)
which we note is defined only for z ≥ 0. Note that the ratio vm (0)
reduces to the Thévenin constant
G∞ . This ratio is current to voltage, so it has units of conductance. Therefore, it is very useful to
think of this ratio as telling us what resistance we see looking into the mouth of the semi-infinite
cable. While heuristic in nature, this will give us a powerful way to judge the capabilities of dendritic
fibers for information transmission.
254
Finally, in the finite cable version, we consider a finite length, 0 ≤ z ≤ `, of cable with current Ie
pumped in at z = and a conductance load of Ge applied at the far end z = `. The cable can be thought
of as a length of fiber whose two ends are capped with membrane that is identical to the membrane that
makes up the cable. The load conductance Ge represents the conductance of the membrane capping
the cable or the conductance of another cell body attached at that point. The system to solve is now
d2 vm
λ2C = vm , ii (0) = Ie , ii (`) = Ge vm (`).
dz 2
This has solution
`−z G `−z
Ie cosh( λC ) + G∞e sinh( λC )
vm (z) = , 0 ≤ z ≤ `. (14.16)
G∞ sinh( λ`C ) + GiGnfe ty cosh( λ`C )
ii (0)
with Thévenin equivalent conductance vm (0)
given by
sinh( λ`C ) + Ge
G∞
cosh( λ`C )
GT (`) = G∞ , 0 ≤ z ≤ `. (14.17)
cosh( λ`C ) + Ge
G∞
sinh( λ`C )
Now if the end caps of the cable are patches of membrane whose specific conductance is the same as
the rest of the fiber, the surface area of the cap is πa2 which is much smaller than the surface of the
cylindrical fiber, 2πa`. Hence, the conductance of the cylinder without caps is 2πa`GM which is very
large compared to the conductance of a cap, πa2 GM . So little current will flow through the caps and
we can approximate this situation by thinking of the cap as an open circuit (thereby setting Ge = 0).
We can think of this as the open-circuit case. Using equations 14.16 and 14.17, we find
`−z
Ie cosh( λC )
vm (z) = , 0 ≤ z ≤ `. (14.18)
G∞ sinh( λ`C )
`
GT (`) = G∞ tanh( ), 0 ≤ z ≤ `. (14.19)
λC
255
14.2.2 Time Dependent Solutions:
If we look for solutions to the infinite cable model that are time dependent, we must use the full
transient cable equation. The full transient cable equation is given by
∂ 2 vm (z, t) ∂vm
λ2C 2
= vm (z, t) + τM − ro λ2C Qe δ(z, t). (14.20)
∂z ∂t
where the external current term ke is modeled by a time-space impulse of magnitude Qe using a two
dimensional Dirac delta function. By a variety of techniques, this equation can be solved to obtain
 
ro λC Qe 1 ( λzC )2 − t
vm (z, t) = q exp − t  e τM .
 (14.21)
τM t
4π( τM ) 4( τM )
If we apply a current Ie for all t greater than zero, it is possible to apply the superposition principle
for linear partial differential equations and write the solution in terms of a standard mathematical
Rx 2
function, the error function, erf (x) = √2
π 0 e−y dy. Note that this situation is the equivalent of the
steady state solution for the infinite cable with a current impulse applied at z = 0:
 s  
z
ro λC Ie  t | | z |
λC
|
vm (z, t) = erf  + q t  − 1 e λC
4 τM 2 τM
 s  
ro λC Ie  t | λzC | −| z |
+ erf  − q t  + 1 e λC (14.22)
4 τM 2 τM
Although this solution is much more complicated in appearance, note that as t → ∞, we obtain the
usual steady state solution given by equation 14.15. We can use this solution to see how quickly the
voltage due to current applied to the fiber decays. We want to know when the voltage vm decays to
one half of its starting value. This is difficult to do analytically, but if you plot the voltage vm vs. the t
for various cable lengths `, you can read off the time at which the voltage crosses the one half value.
This leads to the important empirical result that the time it takes for the voltage to drop to half of its
256
starting value, t 1 satisfies

2
λC λC
z = 2( )t 1 − . (14.23)
τM 2 2
This gives us a relationship between the position on the fiber, z, and the half-life time. The slope of
this line can then be interpreted as a velocity, the rate at which the fiber position for half-life changes;
this is a conduction velocity and is given by
λC
v 1 = 2( ), (14.24)
2 τM
having units of (cm/sec). Using our standard assumption that ri ro and our equations for λC and
gm in terms of membrane parameters, we find
s
2GM 1
v1 = 2
a2 , (14.25)
2 ρi CM
indicating that the induced voltage attenuates proportional to the square root of the fiber radius a.
Hence, the double the ratio of the fundamental space to time constant is an important heuristic measure
of the propagation speed of the voltage pulse.
The case of a finite cable, 0 ≤ z ≤ ` requires a different set of boundary conditions than we have
seen before. We think of the dendritic cylinder as having end caps made of the same membrane as
its walls. For boundary conditions, we will impose what are called zero-rate end cap potentials–this
means that each end cap is at equipotential: hence the rate of change of the potential vm with respect
to the space variable λ is zero at both ends. Thus, we look the solution to the homogeneous full
transient cable equation
∂ 2 vm (z, t) ∂vm
λ2C = v m (z, t) + τ M , 0 ≤ z ≤ `, t ≥ 0,
∂z 2 ∂t
257
∂v̂m (0, τ ) ∂v̂m (L, τ )

= 0, = 0. (14.26)
∂λ ∂λ
For convenience, we can replace equation 14.26 with a normalized form using the transformations
t z `
τ = , λ= , L= ,
τM λC λC
v̂m = vm (λC λ, τM τ ),
∂ 2 v̂m ∂vm
2
= v̂m + , 0 ≤ z ≤ `, t ≥ 0. (14.27)
∂λ ∂τ
Assuming a solution of the form v̂m (λ, τ ) = u(λ) w(τ ), the technique of separation of variables leads
to the coupled system:
d2 u du du
2
= (1 + β)u, 0 ≤ λ ≤ L, (0) = 0, , (L) = 0, (14.28)
dλ dλ dλ
dw
= βw, τ ≥ 0, (14.29)
dτ
where the separation constant β, determined by looking for nontrivial solutions to equations 14.28
and 14.29, must have the form
β = −1 − αn2 ,
nπ
αn = ,
L
for integers n ≥ 0. This leads to a general solution of the form
2
n
v̂m (λ, τ ) = An cos(αn λ) e−(1+αn )τ . (14.30)
258
This implies that the most general solution is given by
∞
2
v̂m (λ, τ ) = A0 e−τ + An cos(αn λ) e−(1+αn )τ
X
(14.31)
n=1
If we apply voltage data to the finite cable with spatial distribution v̂m (λ, 0) = V (λ), since the
eigenfunctions given by equation 14.30 form a complete or total orthonormal set in the space of
square integrable functions on [0, L], by the superposition principle, we can match the desired voltage
data V using standard Fourier series techniques to obtain:
∞
X
V (λ) = A0 + An cos(αn λ), (14.32)
n=1
1ZL
A0 = V (λ)dλ, (14.33)
L 0
2ZL
An = V (λ) cos(αn λ) dλ. (14.34)
L 0
We are primarily interested in modeling the effect of the brief pulse of charge that is generated by
a synaptic event. We will think of these Post Synaptic Pulses or PSPs as generated by Dirac delta
1 RL
functions which are normalized a bit different: we assume that L 0
δ(λ)dλ = 0. We can show that
if the amount of charge deposited in the PSP is Qe , then a voltage impulse applied at the spatial point
Qe
λ = ξ will be given by V (λ) = λC cm
δ(λ − ξ). This leads to analogs of the Fourier coefficient
equations 14.33 - 14.34 given by
∞
X
V (λ) = A0 + An cos(αn λ), (14.35)
n=1
Qe
A0 = , (14.36)
L λ C cm
An = 2 A0 cos(αn ξ), (14.37)
with solution
259
Figure 14.2: The Ball and Stick Model
∞
2
v̂m (λ, τ ) = A0 eτ + 2A0 cos(αn ξ) cos(αn λ) e−(1+αn )τ .
X
(14.38)
n=1
14.3 The Ball and Stick Model:
We can now extend our model to what is called the ball and stick neuron model which consists of an
isopotential sphere (the soma) coupled to a single dendritic fiber input line. We model the soma as a
simple parallel resistance/ capacitance network and the dendrite as a finite length cable as previously
discussed (see Figure 14.2).
In Figure 14.2, you see the terms I0 , the input current at the soma/ dendrite junction starting at
τ = 0; ID , the portion of the input current that enters the dendrite (effectively determined by the
input conductance to the finite cable, GD ); IS , the portion of the input current that enters the soma
(effectively determined by the soma conductance GS ); and CS , the soma membrane capacitance. We
assume that the electrical properties of the soma and dendrite membrane are the same; this implies
that the fundamental time and space constants of the soma and dendrite are given by the same constant
(we will use our standard notation τM and λC as usual). It takes a bit of work, but it is possible to
show that with a reasonable zero-rate left end cap condition the appropriate boundary condition at
260
λ = 0 is given by
" #
∂v̂m ∂v̂m
ρ (0, τ ) = tanh(L) v̂m (0, τ ) + (0, τ ) , (14.39)
∂λ ∂τ
GD
where we introduce the fundamental ratio ρ = GS
, the ratio of the dendritic conductance to soma
conductance. For more discussion of the ball and stick model boundary conditions we use here, you
can look at the treatments in (Johnston and Wu (8) 1995) and (Rall (10) 1977) . The full system to
solve is therefore:
∂ 2 v̂m ∂vm
2
= v̂m + , 0 ≤ z ≤ `, t ≥ 0. (14.40)
∂λ ∂τ
∂v̂m
(L, τ ) = 0, (14.41)
∂λ " #
∂v̂m ∂v̂m
ρ (0, τ ) = tanh(L) v̂m (0, τ ) + (0, τ ) . (14.42)
∂λ ∂τ
Applying the technique of separation of variables, v̂m (λ, τ ) = u(λ)w(τ ), leads to the system:
u00 (λ)w(τ ) = u(λ)w(τ ) + u(λ)w0 (τ )
ρu0 (0)w(τ ) = tanh(L) (u(0)w(τ ) + u(0)w0 (τ ))
u0 (L)w(τ ) = 0
This leads to the ratio equation
u00 (λ) w0 (τ )
= .
u(λ) w(τ )
Since these ratios hold for all τ and λ, they must equal a common constant β which is called the
261
separation of variables constant. Thus, we have
d2 u
= (1 + β)u, 0 ≤ λ ≤ L, (14.43)
dλ2
dw
= βw, τ ≥ 0. (14.44)
dτ
The boundary conditions then become
u0 (L) = 0
ρu0 (0) − tanh(L)u(0) = 0.
The only case where we can have non trivial solutions to Equation 14.43 occur when 1+β = −α2 for
some constant α. The general solution to Equation 14.43 is then of the form A cos(αλ) + B sin(αλ).
To satisfy the boundary conditions, we find A and B must be chosen to satisfy the system
−α2 tanh(L)A + ραB = 0
−α sin(αL) + α cos(αL) = 0
A non trivial solution requires that the determinant of the system be nonzero. This implies α must
satisfy the transcendental equation
tanh(L)
tan(αL) = −α , = −k(αL), (14.45)
ρ
tanh(L)
where k = ρL
. The values of α that satisfy Equation 14.45 give us the eigenvalue of our original
problem, β = −1 − α2 . The eigenvalues of our system can be determined by the solution of the
transcendental equation 14.45. This is easy to do graphically as you can see in Figure 14.3). It can be
shown that the eigenvalues form a monotonically increasing sequence starting with α0 = 0 and with
262
Figure 14.3: The Ball and Stick Eigenvalue Problem
2n−1
the values αn approaching asymptotically the values 2
π. Hence, there are a countable number of
eigenvalues of the form βn = −1 − αn2 leading to a general solution of the form
2
n
v̂m (λ, τ ) = An cos(αn λ) e−(1+αn )τ . (14.46)
Hence, this system has the eigenvalue/ eigenfunction pairs given by αn (the solution to the transcen-
dental equation 14.45) and cos[αn (L − λ)]. These eigenfunctions are not mutually orthogonal in the
L2 inner product (this system is not a Stürm-Liouville system). In fact, we can show that for n 6= m,
Z L sin((αn + αm )L) sin((αn − αm )L)

cos[αn (L − λ) cos[αm (L − λ) = +
0 αn + αm αn − αm
(2n−1)π
Since lim αn = 2
, we see there is an integer Q so that
263
Z L
cos[αn (L − λ) cos[αm (L − λ) ≈ 0
0
if n and m exceed Q. Thus, as usual, we expect the most general solution is given by
Q ∞
2 2
v̂m (λ, τ ) = A0 e−τ + An cos(αn (L − λ))e−(1+αn )τ + An cos(αn (L − λ))e−(1+α n )τ
X X
(14.47)
n=1 n=Q+1
Since the spatial eigenfunction are approximately orthogonal, the computation of the coefficients An
for n > Q can be handled with a straightforward inner product calculation. The calculation of the
first Q coefficients must be handled as a linear algebra problem.
1 PP 1 RL
Note this gives L j=1 V (j∆)∆ = V0 reflecting the usual normalization L 0
V0 δ(λ − z)dλ = V0 .
The choice of P N helps to insure that we adequately sample the delta function.
14.4 Simplifying Dendritic Arbors:
Consider the stylized soma plus dendritic tree model illustrated in Figure 14.4 (each dendritic fiber
extends infinitely to the right) and Figure 14.5 (each dendritic fiber is of finite length).
The dendritic tree is represented by branching line segments. A typical line segment has radius ai
and at some point branches into several processes (for convenience, we show only double branching).
The final branches in Figure 14.4 terminate in dotted lines indicating that these dendritic trees extend
to infinity. The dendritic tree has a variety branch radii (a0 , a11 , a12 , a211 , a212 , a3111 , a3112 and is
shown with three branch points (X1 , X2 and X3 ). Consider the X3 junction and mentally detach its
two branches. Assume that these two fibers have a sealed end cap condition at X3 (this is z = 0
for them). These two fibers stretch to infinity, so we are in the semi-infinite cable case. The input
conductance to each of these fibers is given by Equation 14.13 where we will denote the geometry
q
2GM
independent constant π ρi
by K for convenience. Thus,
264
Figure 14.4: Soma Plus Dendritic Arbors: Infinite Fibers
Figure 14.5: Soma Plus Dendritic Arbors: Finite Arbors
265
3 3
G3111
∞ = K a3111
2
, G3112
∞ = K a3112
2
,
and if we think of junction X3 as two sealed end cap cables coming together, then the combined input
conductance seen at the junction is
3 3

GX
∞
3
= K a3111
2
+ a3112
2
.
3
Since the input conductance of a semi-infinite fiber emanating from junction X2 is K a211
2
, these
conductances match if the cable radii a211 , a3111 and a3112 satisfy the relationship
3 3 3
a211
2
= a3111
2
+ a3112
2
.
This is a powerful tool for simplifying dendritic arbors. Continuing with arguments of this sort, we
can replace all branched processes with an equivalent single fiber as long as the new fibers radius
satisfies a rule of the following form:
3 X 3
ap2 = ad2 (14.48)
d∈D(p)
where p denotes the parent fiber; D(p), the daughter branches emanating from the parent fiber and d,
3
a given daughter fiber. This rule is known as the Rall 2
Power Rule.
Similar arguments can be made in the case of dendritic arbors where each fiber is of finite length.
We then have to use the finite length cable theory. In Figure 14.5, we see a portion of the same
dendritic arbor shown in Figure 14.4. This time, each fiber of radius ai and length ì is considered
to have space constant λiC so that the fundamental length of each fiber, its electrotonic length, is the
ì
ration λiC
. Hence, this dendritic arbor has branch lengths; (`0 , `11 , `12 , `211 , `212 , `3111 , `3112 and space
266
constants; (λ0C ,
lambda11 12 211 212 3111 3112
C , λC , λC , λC , λC , λC . At branch point X3 , for sealed end cap conditions, the input
conductance of the finite cable is given by
!
`3111 3 `3111
G∞ ( 3111 ) = Ka3111
2
tanh 3111
λC λC
!
`3112 3 `3112
G∞ ( 3112 ) = Ka3112 tanh 3112
2
λC λC
with the total input conductance seen at X3 given by
( ! !)
3 `3111 3 `3112
GX
∞
3
= K a3111 2
tanh 3111 + a31122
tanh 3112 .
λC λC
The input conductance at position ` on the cable of radius a211 starting at junction X2 is
!
3 `
GX
∞ (`)
2
= Ka211 tanh
2
.
λ211
C
The junction X3 occurs at position `211 along this fiber. These conductances are therefore equal when
! ! !
3 `211 3 `3111 3 `3112
a211
2
tanh 211 = a3111
2
tanh 3111 + a3112
2
tanh 3112 . (14.49)
λC λC λC
3
While this is not true in general, if we assume that Rall’s 2
power rule holds and if we assume that
all length to space constant rations are constant; that is, there is a constant electrotonic length L̂ such
that for all dendritic processes i in the arbor
267
ì
= L̂.
λiC
Under the constant electrotonic length assumption, equation 14.49 simplifies to
3 3 3
a211
2
= a3111
2
+ a3112
2
,
which holds by Rall’s 23 power rule. We can continue this process at each junction eventually reducing
the original dendritic arbor to a single cable of radius a0 with
3 3 3
a02 = a11
2
+ a12
2
3 3 3
a11
2
= a211
2
+ a212
2
3 3 3
a211
2
= a3111
2
+ a3112
2
and
`0 `11 `211 `3111

= = 211 = 3111 = L̂
λ0C 11
λC λC λC
Hence, our single cable has electronic length 4L̂ and the input conductance at any point ` along its
length is given by
!
` 3
G∞ (`) = Ka0 tanh 0 2
. (14.50)
λC
A nice graphical way of looking at it is shown in Figure 14.6. Each circle has radius one electronic
unit. Hence, junctions falling on a circle of radius of L̂ = i will all have the same input conductance
268
Figure 14.6: Input Conductance in Finite Cable Rall Theory
as given by Equation 14.50.
269
270
Chapter 15
The Diffusion Equation:
The full cable equation
∂ 2 vm ∂vm
λ2c 2
= v m + τm − ro λ2c ke ,
∂z ∂t
where ke is current per unit length can be converted into a simpler partial differential equation called
a diffusion equation with a change of variables. First, we introduce a dimensionless scaling to make it
z t
easier via the change of variables: y = λc
and s = τm
. With these changes, space will be measured in
units of space constants and time in units of time constants. We then define the a new voltage variable
w by
w(s, y) = vm (τm t, λc z)
It is then easy to show using the chain rule that
∂2w 2
2 ∂ vm
= λ c
∂y 2 ∂z 2
∂w ∂vm
= τm
∂s ∂t
271
giving us the scaled cable equation
∂2w ∂w
2
= w + − ro λ2c ke (τm s, λc y)
∂y ∂s
Now to further simplify our work, let’s make the additional change of variables
Φ(s, y) = w(s, y) es
Then
∂Φ ∂w
= ( + w) es
∂s ∂s
∂2Φ ∂2w s
= e
∂y 2 ∂y 2
leading to
∂ 2 Φ −s ∂Φ −s
2
e = e − r0 λ2c ke (τm s, λc y)
∂y ∂s
After rearranging, we have the version of the transformed cable equation we need to solve:
∂2Φ ∂Φ
2
= − r0 λ2c τm ke (τm s, λc y) es (15.1)
∂y ∂s
Recall that ke is current per unit length. We are going to show you a physical way to find a solution
to the above diffusion equation when there is an instantaneous current impulse of strength I0 applied
at some nonnegative time t0 and nonnegative spatial location z0 . Essentially, we will think of this
instantaneous impulse as a Dirac delta function input as we have discussed before: i.e., we will need
272
Figure 15.1: Walking In a Volume Box
to solve
∂2Φ ∂Φ
2
= − ro λ2c I0 δ(s − s0 , y − y0 ) es
∂y ∂s
In this chapter, we will show how we can reason out what the solution to this equation looks like and
its qualitative behavior relative to the important physical constants λc and τm .
15.1 The Microscopic Space-Time Evolution of a Particle:
The simplest probabilistic model that links the Brownian motion of particles to the macroscopic laws
of diffusion is the 1D random walk model . In this model, we assume a particle moves every τm
seconds along the y axis a distance of either λc or −λc with probability 12 . Consider the thought
experiment shown in Figure 15.1 where we see a volume element which has length 2λc and cross
sectional area A. Since we want to do microscopic analysis of the space time evolution of the particles,
we assume that λc < y.
Let φ+ (s, y) denote the flux density of particles crossing from left to right across the plane located
at position y at time s; similarly, let φ− (s, y) be the flux density of particles crossing from right to left.
Further, c(s, y) denote the concentration of particles at coordinates (s, y). What is the net number of
particles that cross the plane of area A?
Since the particles randomly change their position every τ seconds by ±λc , we can calculate flux
273
as follows: first, recall that flux here is the number of particles per unit area and time; i.e., the units
particles
are sec−cm2
. Since the walk is random, half of the particles will move to the right and half to the left.
λc
Since the distance moved is λc , half the concentration at c(y − 2
, s) will move to the right and half
the concentration at c(y + λ2c , s) will move to the left. Now the number of particles crossing the plane
is concentration times the volume. Hence, the flux terms are
1 Aλc c(y − λ2c , s)

φ+ (s, y) =
2 Aτm
λc λc
= c(y − , s)
2τm 2
− 1 Aλc c(y + λ2c , s)
φ (s, y) =
2 Aτm
λc λc
= c(y + , s)
2τm 2
The net flux, φ(s, y) is thus
φ(s, y) = φ+ (s, y) − φ− (s, y)

λc λc λc
= (c(y − , s) − c(y + , s))
2τm 2 2
λc
Since, y
is very small in microscopic analysis, we can approximate the concentration c using a first
order Taylor series expansion in two variables if we assume that the concentration is sufficiently
smooth. Our knowledge of the concentration functions we see in the laboratory and other physical
situations implies that it is very reasonable to make such a smoothness assumption. Hence, for small
perturbations s + a and y + b from the base point (s, y), we find
∂c ∂c
c(s + a, y + b) = c(s, y) + (s, y) a + (s, y) b + e(s, y, a, b)
∂s ∂y
where e(s, y, a, b is an error term which is proportional to the size of the largest of |a| and |b|. Thus, e
goes to zero as (a, b) goes to zero in a certain way. In particular, for a = 0 and b = ± λ2c , we obtain
274
λc ∂c λc λc
c(s, y − ) = c(s, y) − (s, y) + e(s, y, 0, − )
2 ∂y 2 2
λc ∂c λc λc
c(s, y + ) = c(s, y) + (s, y) + e(s, y, 0, )
2 ∂y 2 2
and we note that the error terms are proportional to λ2c Thus,
λc ∂c λc λc
φ(s, y) = − (s, y)) λc + (e(s, y, 0, − ) − e(s, y, 0, ))
2τm ∂y 2 2
λ2 ∂c
≈ − c (s, y)
2τm ∂y
as the difference in error terms is still proportional to λ2c at worst and since λc is very small compared
to y, the error term is negligible.
Recall from Chapter 5, that Ficke’s law of diffusion for particles across a membrane (think of our
plane at y as the membrane) is given by Equation (5.1) which is written as
∂ [b]
Jdif f = −D
∂x
Equating c with [b] and Jdif f with φ, we see that the diffusion constant D in Ficke’s Law of diffusion
can be interpreted in this context as
λ2c
D =
τm
This will give us a powerful connection between the macroscopic diffusion coefficient of Ficke’s Law
with the microscopic quantities that define a random walk as we will see in the next section.
275
Figure 15.2: The Random Walk Of A Particle
15.2 The Random Walk And The Binomial Distribution:
In this section, we will be following the discussion presented in Weiss (Weiss (12) 1996) , but para-
phrasing and simplifying it for our purposes. More details can be gleaned from a careful study of that
volume. Let’s assume that a particle is executing a random walk starting at position x = 0 and time
t = 0. This means that from that starting point, the particle can move either +λc or −λc at each
tick of a clock with time measured in time constant units τm . We can draw this as a tree as shown in
Figure 15.2.
In this figure, the labels shown in each node refer to three things: the time, in units of the time
constant τm (hence, t = 3 denotes a time of 3τm ); spatial position in units of the space constant
λc (thus, x = −2 means a position of −2λc units); and the number of possible paths that read that
node (therefore, Paths equal to 6 means there are six possible paths that can be taken to arrive at that
terminal node.
Since time and space are discretized into units of time and space constants, we have a physical
system where time and space are measured as integers. Thus, we can ask what is the probability,
W (m, n), that the particle will be at position m at time n. In the time interval of n units, let’s define
some auxiliary variables: n+ is the number of time steps where the particle moves to the right – i.e.,
the movement is +1; and n− is the number of time steps the particle moves to the left, a movement of
−1. We clearly see that M is really the net displacement and
n = n+ + n−
m = n= − n−
276
Solving, we see
n + m
n+ =
2
n − m
n− =
2
Let the usual binomial coefficients be denoted by Bn,j where
 
 n  n!
Bn,j =   =
 
j j! (n − j)!
Now look closely at Figure 15.2. At a given node, all of the paths that can be taken to that node have
the same n+ value as shown in Table 15.1:
Time Paths n+ Binomial Coefficient Bn,n+

1 1-1 0-1 B1,0 - B1,1
2 1-2-1 0-1-2 B2,0 - B2,1 - B2,2
3 1-3-3-1 0-1-2-3 B3,0 - B3,1 - B3,2 - B3,3
4 1-6-4-6-1 0-1-2-3-4 B4,0 - B4,1 - B4,2 - B4,3 - B4,4
Table 15.1: Comparing Paths And Rightward Movements
15.3 Rightward Movement Has Probability 0.5 Or Less:
Let the probability that the particle moves to the right be p and the probability it moves to the left be
q. Then we have p + q = 1. Let’s assume that p ≤ 0.5. This forces q ≥ 0.5. Then, in n time units,
the probability a given path of length n is taken is ρ(n) where
+ − + +
ρ(n) = pn q n = pn q n − n
and the probability that a path will terminate at position m, W (m, n), is just the number of paths that
277
reach that position in n time units multiplied by ρ(n). We know that for a given number of time steps,
certain position will never be reached. Note that if the fraction 0.5(n + m) is not an integer, then there
will be no paths that reach that position m. Let nf be the results of the computation nf = 0.5(n + m).
We know nf need not be an integer. Define the extended binomial coefficients Cn,nf by

 Bn,n if nf is an integer


f
Cn,nf =
 0 else


Then, we see
W (m, n) = Cn,nf pnf q n − nf
From our discussions above, it is clear for any position m that is reached in n time units, that this can
be rewritten in terms of n+ as
+ (m) + (m)
W (m, n) = Bn,n+ (m) pn qn − n
where n+ (m) is the value of n+ associated with paths terminating on position m. If you think about
this a bit, you’ll see that for even times n, only even positions m are reached; similarly, for odd times,
only odd positions are reached.
15.3.1 Finding The Average Of The Particles Distribution In Space And Time:
The average position m is defined by
278
mX
=n
m = mW (m, n)
m = −n
where of course, many of the individual terms W (m, n) are actually zero for a given time n because
the positions are never reached. From this, we can infer that
n+ =n
+ +
m Bn,n+ pn q n − n
X
m =
n+ = 0
To compute this, first, switch to a simple notation. Let j = n+ . Then, we note that we have, for
m = 2n+ − n or m = 2j − n,
jX
=n
m = m Bn,j pj q n − j
j=0
jX
=n
= (2j − n) Bn,j pj q n − j
j=0
= 2jnS
where
jX
=n
j = j Bn,j pj q n − j
j=0
jX
=n
S = Bn,j pj q n − j
j=0
Since p + q = 1, we know that
jX
=n
(p + q) n
= = S = Bn,j pj q n − j = 1
j=0
279
Further, by taking derivatives with respect to p, we see that
d
p ((p + q)n ) = p n (p + q)n−1 = p n
dp
Thus,
jX
=n
j = j Bn,j pj q n − j
j=0
jX
=n
= j p Bn,j pj−1 q n − j
j=0
jX
=n
d
= p Bn,j pj q n − j
j=0 dp
 
jX
=n
d 
= p Bn,j pj q n − j 
dp j = 0
d
= p ((p + q)n )
dp
= pn
by our calculations above. We conclude that
m = 2jnS
= 2pn − n
15.3.2 Finding The Standard Deviation Of The Particles Distribution In Space
And Time:
We compute the standard deviation of our particle’s movement through space and time in a similar
way. We need to find
280
mX
=n
σ2 = m2 W (m, n)
m = −n
Our earlier discussions still apply and we find we can rewrite this as
jX
=n
σ2 = (2j − n)2 Bn,j pj q n − j
j=0
jX
=n
= (4j 2 − 4jn + n2 ) Bn,j pj q n − j
j=0
= 4j 2 − 4 n j + n2 S
Where j 2 is the standard deviation squared of the usual binomial distribution. We know S is 1 and j
is pn. So we only have to compute j 2 . Note that
d2
p2 ((p + q)n
) = p 2
n (n − 1) (p + q)n−2
= p2 n (n − 1)
d2 p
Also,
d2
p2 n (n − 1) = p2 ((p + q)n )
d2 p
 
d2 jX
=n
= p2 2  Bn,j pj q n − j 
d p j=0
jX
=n
d2 j n−j

= p2 Bn,j p q
j=0 d2 p
jX
=n
= p2 j (j − 1) Bn,j pj−2 q n − j
j=0
jX
=n
= (j 2 − j) Bn,j pj q n − j
j=0
281
= j2 − j
We conclude that
j 2 = p2 n (n − 1) + p n
Since, we also have a formula for σ 2 , we see
σ 2 = 4j 2 − 4 n j + n2 S
= 4(p2 n (n − 1) + p n) − 4 n p n + n2
= n2 − 4p n (1 − p) (n − 1)
= (1 − α)n2 + α n
where α = 4p (1 − p) ranges from 0 to 1 with a global maximum at α = 0.5 or p = 0.5.
15.3.3 Specializing To An Equal Probability Left And Right Random Walk:
Here, p and q are both 0.5. We see that α = 1 and
m = 2pn − n = 0
m2 = (1 − α)n2 + α n = n
Note, that if the random walk is skewed, with say p = 0.1, then we would obtain α = 0.36 and
m = 2 p n − n = −0.8n
m2 = (1 − α)n2 + α n = 0.64n2 + 0.36n
282
so that for large n, the standard deviation of our particle’s movement would be approximately 0.8n
rather than n.
15.4 Macroscopic Scale:
For a very large number of steps, the probability distribution, W (m, n), will approach a limiting form.
This is done by using an approximation to k! that is know as the Stirling Approximation. It is known
that for very large k,
!k
√ k
k! ≈ 2πk .
e
The distribution of our particle’s position throughout space and time can be written as
n+m n−m
W (m, n) = Bn, n+m p 2 q 2
2
using our definitions of n+ and n− (it is understood that W (m, n) is zero for non integer values of
these fractions). We can apply Stirling’s approximation to Bn, n+m :
2
√ n
n
n! ≈ 2πn
e
s n+m
n+m n+m n+m 2

( )! ≈ 2π
2 2 2e
n+m n+m
n m 2
q
2
≈ π(n + m) 1+
2e n
s n−m
n−m n−m n−m 2

( )! ≈ 2π
2 2 2e
n−m n−m
q n 2 m 2
≈ π(n − m) 1−
2e n
283
From this, we find
s !n −m m
m2
n
n+m n−m m2 n 2
m m

2 2
! ! ≈ πn 1− 2 1− 2 1− 1+
2 2 n 2e n n n
Hence, we see
√ ! −1 ! −n m −m
m2 m2
−n
2πn n n n 2 2
m m

2 2
Bn, n+m ≈ ) 1− 2 1− 2 1− 1+
2 πn e 2e n n n n
s ! −1 ! −n m −m
2 n m2 2
m2 2
m 2 m 2
≈ 2 1− 2 1− 2 1− 1+
πn n n n n
Thus,
m2 m2
! !
1 2 −1 −n

ln Bn, n+m ≈ ln + n ln(2) + ln 1 − 2 + ln 1 − 2
2 2 πn 2 n 2 n
m m −m m

+ ln 1 − + ln 1 +
2 n 2 n
m
Now, for small x, the standard Taylor’s series approximation gives ln(1 + x) ≈ x; hence, for n
sufficiently small, we can say
1 2 1 m2 n m2 m m m m

ln Bn, n+m ≈ ln + n ln(2) + 2
+ 2
− −
2 2 πn 2 n 2 n 2 n 2 n
1 2 1 m2 m2

≈ ln + n ln(2) + −
2 πn 2 n2 2n
m2
For very large n (i.e. after a very large number of time steps nτm ), since |m| ≤ n, the term n2
is
negligible. Hence dropping that term and exponentiating, we find
284
s
−m2
!
2
Bn, n+m ≈ exp 2n
2 nπ 2n
This implies that
s
−m2
!
2 n+m n−m
W (m, n) ≈ exp 2n p 2 q 2
nπ 2n
s !m
−m2
!
2 n p 2
≈ exp (4pq) 2
nπ 2n q
Note that if the particle moves with equal probability 0.5 to the right or the left at any time tick, this
reduces to
s
−m2
!
2
W (m, n) ≈ exp
nπ 2n
1 2
and for p = 3
and q = 3
, this becomes
s ! n m
2 −m2 8 2 1 2
W (m, n) ≈ exp
nπ 2n 9 2
15.5 Leftward Movement Has Probability 0.5 Or Less:
In this case, the roles of p and q are reversed. However, the discussion and analysis remains the same.
We obtain
s !m
−m2
!
2 n q 2
W (m, n) ≈ exp (4pq) 2
nπ 2n p
q
Note that the term p
is less than or equal to 1 and hence, the terms W (m, n) exhibit decay as m and
285
n grow.
15.6 Obtaining The Probability Density Function:
From our discrete approximations in previous sections, we can now derive the probability, P (x, t),
that the particle will be at position x at time t. In what follows, we will assume that p ≤ 0.5. Let ∆x
be a small number which is approximately mλc for some m. The probability that the particle is in an
∆x ∆x
interval [x − 2
,x + 2
] can then be approximated by
X
P (x, t) ∆x ≈ W (k, n)
k
where the sum is over all indices k such that the position kλc lies in the interval [− ∆x
2
, ∆x
2
]. Hence,
∆x ∆x
[− , ] ≡ {(m − j)λc , ..., mλc , ..., (m + j)λc }
2 2
for some integer j. Now from the way the particle moves in a random walk, only half of these tick
marks will actually be positions the particle can occupy. Hence, half of the probabilities W (m − i, n)
∆x
for i from −j to j are zero. The number of nonzero probabilities is thus ≈ 2λc
. We can therefore
approximate the sum by taking the middle term W (m, n) and multiplying by the number of nonzero
probabilities.
∆x
P (x, t) ∆x ≈ W (m, n)
2λc
which implies, since x = mλc and t = nτm , that for very large n,
1
P (x, t) = W (m, n)
2λc
286
  x
−x2
!
1 t p 2λc
= q 2
exp  λ2  (4pq) 2τm
4π τλmc t 4 2τcm t q
λ2c
Note that the term 2τm
is the diffusion constant D. Thus,
x
−x2
! !
1 t p 2λc
P (x, t) = √ exp (4pq) 2τm
4πD t 4D t q
Next, rewrite all the power terms as exponentials:
−x2
! !
1 t p x

P (x, t) = √ exp exp ln(4pq) exp ln( )
4πD t 4D t 2τm q 2λc
Note since p + q = 1, 4pq is between bigger than zero and strictly less than 1 for all nonzero p and
q with p not 0.5. Hence, A is always negative unless the random walk is equal probability to left and
1
right. Let ξ be the value 4pq
. Then, ξ is bigger than one and
!
t −t −t ln(ξ))
(4pq) 2τm = (ξ) 2τm = exp
2τm
Also, since p is less than 0.5, A is less than 1. Let ζ be the value pq . Then,
! x !
p 2λc −x −x ln(ζ))
= (ζ) 2λc = exp
q 2λc
Rewriting the density function, we obtain
287
−x2
!
1 t x
P (x, t) = √ exp − ln(ξ) − ln(ζ)
4πD t 4D t 2τm 2λc
Letting A = ln(ξ) and B = ln(ζ), from our discussions above, we know both A and B are larger
than 1. We thus have
−x2
!
1 t x
P (x, t) = √ exp − A − B
4πD t 4D t 2τm 2λc
After manipulation, we can complete the square on the quadratic term and rewrite it as
2
−x2 t x 1 BD B 2 − 2A

− A − B = − x + t + t
4D t 2τm 2λc 4Dt λc 4τm
and thus
2 !
B 2 − 2A
!
1 1 BD

P (x, t) = √ exp − x + t exp t
4πD t 4Dt λc 4τm
15.6.1 Special Cases:
The equal probability random walk has A and B zero and therefore generates the probability density
function
x2
!
1
P (x, t) = √ exp −
4πD t 4Dt
1 B 2 − 2A
On the other hand, for p = 6
, we find A = 0.59 and B = 1.61 and so 4
is 0.35 giving the
density
288
2 !
1 1 1.61Dt 0.35t

P (x, t) = √ exp − x + exp
4πD t 4Dt λc τm
1 B 2 − 2A
Similarly, if p = 30
, we find A = 2.05 and B = 3.36 and so 4
is 1.81 giving the density
2 !
1 1 3.36Dt 1.81t

P (x, t) = √ exp − x + exp
4πD t 4Dt λc τm
15.7 Understanding The Probability Distribution Of The Parti-
cle:
It is important to get a strong intuitive feel for the probability distribution of the particle under the
random walk and skewed random walk protocols. A normal distribution has the form
x2
!
1
P (x) = √ exp − 2 )
2πσ 2σ
In Figure 15.3, we see a plot of a particle’s position probability as a function of position for three
different standard deviations, σ. In the plot, the standard deviation is labeled as D.
Now if we skew the distribution so that the probability of moving to the right is now 16 , we find
2 !
1 1 1.61Dt 0.35t

P (x, t) = √ exp − x − exp
4πD t 4Dt λc τm
which generates the plot shown in Figure 15.4.
289
Figure 15.3: Normal Distribution: Spread Depends on Standard Deviation
Figure 15.4: Skewed Random Walk Probability Distribution: p is 0.1666
290
Chapter 16
The Time Dependent Cable Solution:
Recall the full cable equation
∂ 2 vm ∂vm
λ2c 2
= v m + τm − ro λ2c ke
∂z ∂t
Recall that ke is current per unit length. We are going to show you a mathematical way to solve the
above cable equation when there is an instantaneous current impulse applied at some nonnegative
time t0 and nonnegative spatial location z0 . Essentially, we will think of this instantaneous impulse as
a Dirac delta function input as we have discussed before: i.e. we will need to solve
∂ 2 vm ∂vm
λ2c 2
= v m + τm − ro λ2c Ie δ(t − t0 , z − z0 )
∂z ∂t
where δ(t − t0 , z − z0 ) is a Dirac impulse applied at the ordered pair (t0 , z0 ). We will simplify our
reasoning by thinking of the impulse applied at (0, 0) as we can simply translate our solution later as
we did before for the idealized impulse solution to the time independent cable equation.
291
16.1 The Solution For A Current Impulse:
We assume that the cable is infinitely long and there is a current injection at some point z0 on the
cable which instantaneously delivers I0 amps of current. As usual, we will model this instantaneous
delivery of current using a family of pulses. For convenience of exposition, we will consider the point
of application of the pulses to be z0 = 0.
16.1.1 Modeling The Current Pulses:
Consider the two parameter family of pulses below:
2 2
I0 nm n2 t2τ2 −τ
m
2
2λc
2 2 2
Pnm (t, z) = e m e m z −λc
τm λc γ 2
amp
At this point, γ is a constant to be determined. Note that Pnm is measured in cm−sec
. We know the
amp
currents ke have units of cm
; hence, we model the family of current impulses kenm by
kenm (t, z) = τm Pnm (t, z)
This gives us the proper units for the current impulses. This is then a specific example of the type of
pulses we have used in the past. There are several differences:
• Here we give a specific functional form for our pulses which we did not do before. It is straight-
forward to show that these pulses are zero off the (t, z) rectangle [− τnm , τnm ] × [− λmc , λmc ] and are
infinitely differentiable for all time and space points. Most importantly, this means the pulses
are very smooth at the boundary points t = ± τnm and z = ± λmc . Note we are indeed allowing
these pulses to be active for a small interval of time before zero. When we solve the actual cable
problem, we will only be using the positive time portion.
• The current delivered by this pulse is obtained by the following integration:
292
Z ∞ Z ∞
J = Pnm (t, z)dtdz
−∞ −∞
Z λc Z τm
m n
= Pnm (t, z)dtdz
− λmc − τn
m
Since we will be interested only in positive time, we will want to evaluate
λc τm
J Z
m
Z
n
= Pnm (t, z)dtdz
2 − λmc 0
The constant γ will be chosen so that these integrals give the constant value of J = 2I0 for all
n and m. If we integrate over the positive time half of the pulse, we will then get the constant
I0 instead.
amps amp
• The units of our pulse are cmsec
. The time integration then gives us cm
and the following
spatial integration gives us amperes.
Let’s see how we should choose γ: consider
Z λc Z τm
m n
J = Pnm (t, z)dtdz
− λmc − τn
m
nt mz
Make the substitutions β1 = τm
and β2 = λc
. We then obtain with a bit of algebra
τm λc Z 1 Z 1 I0 nm β22−1 β22−1
J = e 1 e 2 dβ1 dβ2
nm −1 −1 τm λc γ 2
!
I0 Z 1 β22−1 Z 1 2
β 2 −1
= 2 e 1 dβ1 e 1 dβ2
γ −1 −1
Z 1 2
I0 2
= 2 e x −1 dx
2
γ −1
Clearly, if we choose the constant γ to be
293
1 Z 1 x22−1
γ = √ e dx
2 −1
then all full pulses Pnm deliver 2I0 amperes of current when integrated over space and time and all
pulses with only nonnegative time deliver I0 amperes.
16.1.2 Scaling the Cable Equation:
Following the discussions in Chapter 15, we can convert cable equation into the scaled version. Recall,
z t
we introduce the changes of variables: y = λc
and s = τm
. and define the new voltage variable w
by
w(s, y) = vm (τm t, λc z)
This gives the scaled equation
∂2w ∂w
2
= w + − ro λ2c ke (τm s, λc y)
∂y ∂s
In particular, for our family of pulses, we have
∂2w ∂w
2
= w + − ro λ2c τm Pnm (τm s, λc y)
∂y ∂s
and since we know the functional form of Pnm , we have
2 2
I0 nm n2 τ 22τsm2 −τ 2 m2 λ2λ c
2 y 2 −λ2
Pnm (τm s, λc y) = e m m e c c
τm λc γ 2
294
I0 nm n2 s22 −1 m2 y22 −1
= e e
τ m λc γ 2
Then, introducing the further change of variables
Φ(s, y) = w(s, y) es
we find
∂2Φ ∂Φ
2
= − r0 λ2c τm Pnm (τm s, λc y) es (16.1)
∂y ∂s
16.1.3 Applying the Laplace Transform In Time:
We will apply some rather sophisticated mathematical tools to solve the Equation (16.1).
The Laplace transform acts on the time domain of a problem as follows: give the function x defined
on s ≥ 0, we define the Laplace Transform of x to be
Z ∞
L(x) = x(s) e−βs ds
0
The new function L(x) is defined for some domain of the new variable β. The variable β’s domain
is called the frequency domain and in general, the values of β where the transform is defined depend
on the function x we are transforming. Also, in order for the Laplace transform of the function x to
work, x must not grow to fast - roughly, x must decay like an exponential function with a negative
coefficient. The solutions we seek to our cable equation are expected on physical grounds to decay
to zero exponentially as we let t (and hence s) go to infinity and as we let the space variable z (and
hence w) go to ±∞. Hence, the function Φ we seek will have a well-defined Laplace transform with
respect to the s variable.
Now, what about the Laplace transform of a derivative? Consider
295
Z ∞
dx dx −βs
L( ) = e ds
ds 0 ds
Integrating by parts, we find
∞ dx −βs Z ∞
−βs ∞
Z
e ds = x(s) e + β x(s) e−βs ds
0 ds 0 0
= lim (x(R) e−βR ) − x(0) + β L(x)

R→∞
Now if the function x grows slower than some e−cR for some constant c, the limit will be zero and we
obtain
dx
L( ) = β L(x) − x(0)
ds
Hence, applying the Laplace transform to both sides of Equation (15.1) we have
∂2Φ ∂Φ
L( 2 ) = L( ) − r0 λ2c L(Pnm (τm s, λc y) es )
∂y ∂s
2
∂ L(Φ)
2
= β L(Φ) − Φ(0, y) − r0 λ2c τm L(Pnm (τm s, λc y) es )
∂y
This is just the transform of the time portion of the equation. The space portion has been left alone.
We will now further assume that
Φ(0, y) = 0, y 6= 0
This is the same as assuming
296
vm (0, z) = 0, z 6= 0
which is a reasonable physical initial condition. This gives us
∂ 2 L(Φ)
= β L(Φ) − r0 λ2c τm L(Pnm (τm s, λc y) es )
∂y 2
16.1.4 Applying the Fourier Transform In Space:
To handle the space portion of the function, we will use the Fourier Transform. Given a function g
defined on the y axis, we define the Fourier Transform of g to be
Z ∞
F(g) = g(y) e−jξy dy
−∞
where j denotes the square root of minus 1 and the exponential term is defined to mean
e−jξy = cos(ξy) − jsin(ξy)
To properly understand this transform, you need to have studied what is called complex analysis
as this integral is a complex line integral, but for our purposes it suffices to note that for decaying
functions of the type we expect Φ to be, this integral will be well-defined.
Note that we can compute the Fourier Transform of the derivative of g as follows:
Z ∞
dg dg −jξy
F( ) = e dy
dy −∞ dy
Integrating by parts, we find
297
∞ dg −jξy Z ∞
−jξy ∞
Z
e dy = g(y) e + jξ g(y) e−jξy dy
−∞ dy −∞ −∞
= lim (g(R) e−jξR ) − lim (g(R) e−jξR ) + jξ F(g)

R→∞ R→−∞
Since we assume that the function g decays sufficiently quickly as y → ±∞, the first term vanishes
and we have
Z ∞ dg −jξy
e dy = +jξ F(g)
−∞ dy
Applying the same type of reasoning, we can see that
∞
Z ∞ d2 g −jξy dg −jξy Z ∞
dg −jξy
e dy = e + jξ e dy
dy 2

−∞ dy
−∞ −∞ dy
dg dg dg
= lim ( (R) e−jξR ) − lim ( (R) e−jξR ) + jξ F( )
R→∞ dy R→−∞ dy dy
We also assume that the function g’s derivative decays sufficiently quickly as y → ±∞. Thus the the
first term vanishes and we have
Z ∞ d2 g −jξy dg
2
e dy = +jξ F( )
−∞ dy dy
= j 2 ξ 2 F(g)
= −ξ 2 F(g)
because j 2 = −1. Hence,
d2 g
F( ) = −ξ 2 F(g)
dy 2
298
Now apply the Fourier Transform in space to the equation we obtained after applying the Laplace
Transform in time. We have
∂ 2 L(Φ)
F( ) = β F(L(Φ)) − r0 λ2c τm F(L(Pnm (τm s, λc y) es ))
∂y 2
or
−ξ 2 F(L(Φ)) = β F(L(Φ)) − r0 λ2c τm F(L(Pnm (τm s, λc y) es ))
For convenience, let
T (Φ) = F(L(Φ))
we see we have
−ξ 2 T (Φ)) = β T (Φ) − r0 λ2c τm T (Pnm (τm s, λc y) es )
16.1.5 The T Transform Of the Pulse:
We must now compute the T transform of the pulse term Pnm (τm s, λc y) es . Since the pulse is zero
off the (t, z) rectangle [− τnm , τnm ] × [− λmc , λmc ], we see the (s, y) integration rectangle reduces to
[− n1 , n1 ] × [− m1 , m1 ]. Hence,
Z 1 Z 1
m n
T (Pnm (τm s, λc y) es ) = 1
Pnm (τm s, λc y) es e−βs e−jξy dsdy
−m 0
1 1
Z
m
Z
n I0 nm n2 s22 −1 m2 y22 −1 s −βs −jξy
= e e e e e dsdy
1
−m 0 τm λc γ 2
299
Now use the change of variables ζ = ns and u = my to obtain
Z 1 1
I0 nm ζ22−1 u22−1 τ ζ n − βζ −jξu dζ du
Z
T (Pnm (τm s, λc y) es ) = e e em e n e m
−1 0 τm λc γ 2 n m
Z 1 Z 1
1 I0 2 2 ζ βζ −jξu
= 2
e ζ2 −1 e u2 −1 e n e− n e m dζ du
2 −1 −1 τm λc γ
Note that this implies that
1 Z1 Z1 I0 2 2
lim T (Pnm (τm s, λc y) es ) = e ζ 2 −1 e u2 −1 dζ du
n,m→∞ 2 −1 −1 τm λc γ 2
I0
= 2γ 2
2τm λc γ 2
I0
=
τm λc
16.1.6 The Idealized Impulse T Transform Solution:
For a given impulse Pnm , we have the T transform solution satisfies
−ξ 2 T (Φ)) = β T (Φ) − r0 λ2c τm T (Pnm (τm s, λc y) es )
and so the idealized solution we seek is obtained by letting n and m go to infinity to obtain
I0
−ξ 2 T (Φ)) = β T (Φ) − r0 λ2c τm
τm λc
= β T (Φ) − r0 λc I0
or
300
(ξ 2 + β)T (Φ)) = r0 λc I0
or finally
Φ∗ = T (Φ))
1
= r0 λc I0
β + ξ2
where for convenience, we denote the T transform of Φ by Φ∗ .
16.1.7 Inverting The T Transform Solution:
To move back from the transform (β, ξ) space to our original (s, y) space, we apply the inverse of our
T transform. For a function h(β, ξ), this is defined by
−1 1 Z∞Z∞
T (h) = h(β, ξ) eβs ejξy dβdξ
2π −∞ 0
To find the solution to our cable equation, we will apply this inverse transform to Φ.
Consider the Laplace Transform of the simple function

 e−as s ≥ 0


f (s) = 
  0 s < 0
where a is positive. It is easy to show that
Z ∞
L(f ) = e−as eβs dts
0
301
1
=
β + a
Hence,
Z ∞ 1 2 r0 λc I0 1
r0 λc I0 2
e−ξ s eβs dβ =
0 β + ξ 2 β + ξ2
Thus, we can compute the inner inverse Laplace transform to obtain
Z ∞ Z ∞ !
−1 ∗ 1 1
T (Φ ) = r0 λc I0 eβs dβ ejξy dξ
2π −∞ 0 β + ξ2
r0 λc I0 Z ∞ −ξ2 s jξy
= e e dξ
2π −∞
r0 λc I0 Z ∞ −ξ2 s + jξy
= e dξ
2π −∞
Now to invert the remaining part, we rewrite the exponent by completing the square:
!
ξ jy jy
−ξ s + jξy = −s ξ − j ξ + ( )2 − ( )2
2 2
s 2s 2s
jy jy

= −s (ξ − )2 − ( )2
2s 2s
Hence,
2s jy 2 y2
e−ξ + jξy
= e−s(ξ − 2s ) e− 4s
because j 2 = −1.
To handle the inversion here, we note that for any positive a and positive base points x0 and y0 :
302
Z ∞ Z ∞ Z ∞ Z ∞ 1
−a(x−x0 )2 −a(y−y0 )2 2 2
e e dxdy = e−u e−v dudv
−∞ −∞ −∞ −∞ a
√ √
using the change of variables u = a(x − x0 ) and v = a(y − y0 ).
Now we convert to polar coordinates to find
Z ∞ Z ∞ 2 2 1 1 Z ∞ Z 2π −r2
e−u e−v dudv = e rdrdθ
−∞ −∞ a a 0 0
π
=
a
This implies that
∞ 2
π
Z
−a(x−x0 )2
e dx =
−∞ a
or
∞ π
Z r
2
e−a(x−x0 ) dx =
−∞ a
We can apply this result to our problem to see
r0 λc I0 Z ∞ −ξ2 s + jξy r0 λc I0 Z ∞ −s(ξ − jy )2 − y2

e dξ = e 2s e 4s dξ
2π −∞ 2π −∞
r0 λc I0 π − y2
r
= e 4s
2π s
1 y2
= r0 λc I0 √ e− 4s
4πs
Hence, our idealized solution is
303
1 y2
Φ(s, y) = r0 λc I0 √ e− 4s
4πs
which tells us that
w(s, y) = Φ(s, y) e−s

1 y2
= r0 λc I0 √ e− 4s e−s
4πs
We can write this in the unscaled form at pulse center (t0 , z0 ) as
z−z0 2
( )
λ2
c
1 − t−t0 t−t0
vm (t, z) = r0 λc I0 q (t−t0 )
e 4( τ
m
)
e−( τm
)
(16.2)
4π τm
16.1.8 A Few Computed Results:
We can use the scaled solutions to generate a few surface plots. In Figure 16.1 we see a pulse applied
at time zero and spatial location 1.0 of magnitude 4.
We can use the linear superposition principle to sum two applied pulses: in Figure 16.2, we see the
effects of a pulse applied at space position 1.0 of magnitude 4.0 add to a pulse of strength 10.0 applied
at position 7.0.
Finally, we can take the results shown in Figure 16.2 and simply plot the voltage at position 10.0 for
the first three seconds. This is shown in Figure 16.3.
16.1.9 Reinterpretation In Terms of Charge:
Note that our family of impulses are
kenm (t, z) = τm Pnm (t, z)
304
Figure 16.1: One Time Dependent Pulse
Figure 16.2: Two Time Dependent Pulses
305
Figure 16.3: Summed Voltage at 3 Time and 10 Space Constants
2 2 !
I0 nm n2 t2τ2 −τ
m
2
2λc
2 2 2
= τm 2
e m e m z −λc
τm λc γ
2 2
(τm I0 )nm n2 t2τ2 −τ
m
2
2λc
2 2 2
= 2
e m e m z −λc
τm λc γ
2 2λ2
(Q0 )nm n2 t2τ2 −τ
m
2
c
m2 z 2 −λ2
= e m e c
τm λc γ 2
where Q0 is the amount of charge deposited in one time constant. The rest of the analysis is quite
similar. Thus, we can also write our solutions as
z−z0 2
( )
λ2
c
r0 λc Q0 1 − t−t0 t−t0
vm (t, z) = q e 4( τ
m
)
e−( τm
)
(16.3)
τm 4π (t−t0)
τm
16.2 The Solution To A Constant Current:
Now we need to attack a harder problem: we will apply a constant external current ie which is defined
by
306

 Ie , t > 0


ie (t) = 
  0, t ≤ 0
Recall that we could rewrite this as ie = Ie u(t) for the standard unit impulse function u. Now in a
time interval h, charge Qe = Ie h is delivered to the cable through the external membrane. Fix the
t
positive time t. Now divide the time interval [0, t] into K equal parts using h equals K
. This gives us
a set of K + 1 points {ti }
t
ti = i , 0 ≤ i ≤ K
K
where we note that t0 is 0 and tK is t. This is called a partition of the interval [0, t] which we denote
t
by the symbol PK . Here h is the fraction K
.
Now let’s think of the charge deposited into the outer membrane at ti as being the full amount Ie h
deposited between ti and ti+1 . Then the time dependent solution due to the injection of this charge at
ti is given by
( z2 )2
λc
r0 λc Ie h 1 − t−t t−ti
i
vm (t, z) = q e 4( τ i )
m e−( τm )
τm 4π (t−ti)
τm
and since our problem is linear, by the superposition principle, we find the solution due to charge Ie h
injected at each point ti is given by
( z2 )2
λc
K −
r0 λc Ie h 1 t−t t−ti
4( τ i )
e−( τm )
X
vm (t, z, PK ) = q e m
τm j=0 4π (t−ti )
τm
( z2 )2
λc
K −
r0 λc Ie 1 t−t t−ti
4( τ i )
e−( τm ) (ti+1 − ti )
X
= q e m
τm j=0 4π (t−ti )
τm
307
Now we can reorder the partition PK using
uK−i = t − ti
which gives uK = t and u0 = 0; hence, we are just moving backwards through the partition. Note
that
ti+1 − ti = uK−i − uK−i−1
= h
This relabeling allows us to rewrite the solution as
( z2 )2
K λc
r0 λc Ie 1 − u ui
4( τ i )
e−( τm ) (ui+1 − ui )
X
vm (t, z, PK ) = q e m
τm j=0 4π (ui )
τm
We can do this for any choice of partition PK . Since all of the functions involved here are continuous,
we see that as K → ∞, we obtain the Riemann Integral of the idealized solution for an impulse of
size Ie applied at the point u
( z2 )2
λc
r0 λc Ie 1 − 4( u
e−( τm )
I u
vm (u, z) = q e τm )
τm u
4π τm
leading to
Z t
I
vm (t, z) = vm (u, z) du
0
( z2 )2
t λc
Z
r0 λc Ie 1 − 4( u
e−( τm ) du
u
= q e τm )
τm u
0 4π τm
308
Chapter 17
The Basic Hodgkin - Huxley Model:
Let’s recall the standard setup of our cable model. The salient variables needed to describe what is
happening inside and outside the cellular membrane and to some extent, inside the membrane are
• Vm0 is the rest value of the membrane potential.
0
• Km is the rest value of the membrane current per length density.
• Ke0 is the rest value of the externally applied current per length density.
• Ii0 is the rest value of the inner current.
• Io0 is the rest value of the inner current.
• Vi0 is the rest value of the inner voltage.
• Vo0 is the rest value of the inner voltage.
• ri is the resistance of the inner fluid of the cable.
• ro is the resistance of the outer fluid surrounding the cable.
• gm is the membrane conductance per unit length.
• cm is the membrane capacitance per unit length.
309
Figure 17.1: The Equivalent Electrical Network Model
The membrane voltage can be shown to satisfy the partial differential equation 17.1
∂ 2 Vm
= (ri + ro )Km − ro Ke (17.1)
∂z 2
In the standard core conductor model, the membrane is not modeled at all. We will think more
carefully about the membrane boxes shown in Figure 17.1.
We will replace our empty membrane box by a parallel circuit model. Now this box is really
a chunk of membrane that is ∆z wide. In the first cable model, we assume our membrane has a
constant resistance and capacitance. We know that conductance is reciprocal resistance, so our model
will consist to a two branch circuit: one branch is contains a capacitor and the other, the conductance
element. We will let cm denote the membrane capacitance density per unit length (measured in f ahrad
cm
).
Hence, in our membrane box, the since the box is ∆z wide, we see the value of capacitance should
1
be cm ∆z. Similarly, we let gm be the conductance per unit length (measured in ohm−cm
) for the
membrane. The amount of conductance for the box element is thus gm∆z. In Figure 17.2, we
illustrate our new membrane model. Since this is a resistance - capacitance parallel circuit, it is
traditional to call this an RC membrane model .
310
In Figure 17.2, the current going into the element

is Km (z, t)∆z and we draw the rest voltage for the
membrane as a battery of value Vm0 . We know that
the membrane current, Km , satisfies Equation 17.2:
∂Vm
Km (z, t) = gm Vm (z, t) + cm (17.2)
∂t
Figure 17.2: The RC Membrane Model
In terms of membrane current densities, all of the
above details come from modeling the simple equation
Km = Kc + Kion
where Km is the membrane current density, Kc is the current through the capacitative side of the cir-
cuit and Kion is the current that flows through the side of the circuit that is modeled by the conductance
term, gm . We see that in this model
∂Vm
Kc = c m
∂t
Kion = gm Vm
However, we can come up with a more realistic model of how the membrane activity contributes
to the membrane voltage by adding models of ion flow controlled by gates in the membrane. We
have not done this before. In this chapter, and subsequent ones, we will study intensely increasingly
more sophisticated versions that model the membrane gates as well as diffusion processes inside the
cell that contribute to ion flow across the membrane. Our models will initially be based on work that
Hodgkin and Huxley performed in the 1950’s.
We start by expanding our membrane model to handle potassium, sodium and a all purpose cur-
rent, called leakage current, using a modification of our original simple electrical circuit model of the
311
Figure 17.3: The Membrane and Gate Circuit Model
membrane. We will think of a gate in the membrane as having an intrinsic resistance and the cell
membrane itself as having an intrinsic capacitance as shown in Figure 17.3:
Thus, we expand the single branch of our old circuit model to multiple branches – one for each ion
flow we wish to model. The ionic current consists of the portions due to potassium, Kk , sodium, KN a
and leakage KL . The leakage current is due to all other sources of ion flow across the membrane
which are not being’ explicitly modeled. This would include ion pumps; gates for other ions such
as Calcium, Chlorine; neurotransmitter activated gates and so forth. We will assume that the leakage
current is chosen so that there is no excitable neural activity at equilibrium.
The standard Hodgkin - Huxley model of an excitatory neuron then consists of the equation for
the total membrane current, KM , obtained from Ohm’s law:
∂Vm
KM = c m + KK + KN a + KL (17.3)
∂t
The new equation for the membrane voltage is thus
∂ 2 Vm
= (ri + ro )Km − ro Ke
∂z 2
∂Vm
= (ri + ro ) cm + (ri + ro ) KK + (ri + ro ) KN a + (ri + ro ) KL − ro ke
∂t
which can be simplified to what is seen in Equation 17.5:
312
1 ∂ 2 Vm ro
2
= Km − Ke (17.4)
ri + ro ∂z ri + ro
∂Vm ro
= cm + KK + KN a + KL − Ke (17.5)
∂t ri + ro
17.1 The Voltage Clamped Protocol:
Under certain experimental conditions, we can force the membrane voltage to be independent of the
spacial variable z. In this case, we find
∂ 2 Vm
= 0
∂z 2
which allows us to rewrite Equation 17.6 as follows
dVm ro
cm + KK + KN a + KL − Ke = 0 (17.6)
dt ri + ro
The replacement of the partial derivatives with a normal derivative reflects the fact that in the voltage
clamped protocol, the membrane voltage depends only on the one variable, time t. Since, cm is
capacitance per unit length, the above equation can also be interpreted in terms of capacitance, Cm ,
and currents, IK , IN a , IL and an external type current Ie . This leads to Equation 17.7
dVm ro
Cm + IK + IN a + IL − Ie = 0 (17.7)
dt r i + ro
Finally, if we label as external current, Ie , the term
ro
IE = Ie ,
ri + r o
313
the equation we need to solve under the voltage clamped protocol becomes Equation 17.8.
dVm 1
= (IK + IN a + IL − IE ) (17.8)
dt CM
17.2 The Hodgkin - Huxley Gate Model:
In Figure 17.4, we show an idealized cell with a small portion of the membrane blown up into an
idealized circuit. We see a small piece of the lipid membrane with an inserted gate. We think of
the gate as having some intrinsic resistance and capacitance. Now for our simple Hodgkin - Huxley
model here, we want to model a sodium and potassium gate as well as the cell capacitance. So
we will have a resistance for both the sodium and potassium. In addition, we know that other ions
move across the membrane due to pumps, other gates and so forth. We will temporarily model this
additional ion current as a leakage current with its own resistance. We also know that each ion has
its own equilibrium potential which is determined by applying the Nernst equation. The driving
electomotive force or driving emf is the difference between the ion equilibrium potential and the
voltage across the membrane itself. Hence, if Ec is the equilibrium potential due to ion c and Vm is
the membrane potential, the driving force is Vc − Vm . In Figure 17.4, we see an electric schematic
that summarizes what we have just said. We model the membrane as a parallel circuit with a branch
for the sodium and potassium ion, a branch for the leakage current and a branch for the membrane
capacitance.
From circuit theory, we know that the charge q across a capacitator is q = C E, where C is the
capacitance and E is the voltage across the capicitor. Hence, if the capacitance C is a constant, we
see that the current through the capacitor is given by the time rate of change of the charge
dq dE
= C
dt dt
If the voltage E was also space dependent, then we would write E(z, t) to indicate its dependence on
314
Figure 17.4: The Simple Hodgkin - Huxley Membrane Circuit Model
both a space variable z and the time t. Then the capacitive current would be
dq ∂E
= C
dt ∂t
From Ohm’s law, we know that voltage is current times resistance; hence for each ion c, we can say
Vc = Ic Rc
where we label the voltage, current and resistance due to this ion with the subscript c. This implies
1
Ic = Vc
Rc
= Gc Ic
where Gc is the reciprocal resistance or conductance of ion c. Hence, we can model all of our ionic
currents using a conductance equation of the form above. Of course, the potassium and sodium
conductances are nonlinear functions of the membrane voltage V and time t. This reflects the fact
315
that the amount of current that flows through the membrane for these ions is dependent on the voltage
differential across the membrane which in turn is also time dependent. The general functional form
for an ion c is thus
Ic = Gc (V, t)(V (t) − Ec (t))
where as we mentioned previously, the driving force, V −Ec , is the difference between the voltage
across the membrane and the equilibrium value for the ion in question, Ec . Note, the ion battery volt-
age Ec itself might also change in time (for example, extracellular potassium concentration changes
over time ). Hence, the driving force is time dependent. The conductance is modeled as the product of
a activation, m, and an inactivation, h, term that are essentially sigmoid nonlinearities. The activation
and inactivation are functions of V and t also. The conductance is assumed to have the form
Gc (V, t) = G0 MN A p (V, t) HN A q (V, t)
where appropriate powers of p and q are found to match known data for a given ion conductance.
We model the leakage current, IL , as
IL = gL (V (t) − EL )
where the leakage battery voltage, EL , and the conductance gL are constants that are data driven.
Hence, in terms of current densities, letting gK , gN a and gL respectively denote the ion conductances
per length, our full model would be
KK = gK (V − EK )
KN A = gN a (V − EN a )
316
KL = gL (V − EL )
We know the membrane voltage satisfies:
1 ∂ 2 Vm ∂Vm ro
2
= cm + KK + KN a + KL − Ke
ri + ro ∂z ∂t ri + ro
We can rewrite this as
1 ∂ 2 Vm ∂Vm ro
2
= cm + gK (Vm − EK ) + gN a (Vm − EN a ) + gL (Vm − EL ) − Ke
ri + ro ∂z ∂t ri + ro
17.2.1 Activation and Inactivation Variables:
We assume that the voltage dependence of our activation and inactivation has been fitted from data.
Hodgkin and Huxley modeled the time dependence of these variables using first order kinetics. They
assumed a typical variable of this type, say x, satisfies for each value of voltage, V :
dx(V )
= αx (V ) (1 − x(V )) − βx (V ) x(V )
dt
x(V, 0) = x0 (V )
For convenience of exposition, we usually drop the functional dependence of x on V and just write:
dx
= αx (1 − x) − βx x
dt
x(0) = x0
Rewriting, we see
317
1 dx αx
= − x
αx + βx dt αx + βx
x(0) = x0
We let
1
τx =
αx + βx
αx
x∞ =
αx + βx
allowing us to rewrite our rate equation as
dx
τx = x∞ − x
dt
x(0) = x0
17.3 The Hodgkin-Huxley Sodium and Potassium Model:
Hodgkin and Huxley modeled the sodium and potassium gates as
M ax 3
gN a (V, t) = gN a MN A (V, t) HN A (V, t)
M ax
gK (V, t) = gK HK 4 (V, t)
where the two activation variables, m and n, and the one inactivation variable all satisfy first order
kinetics as we have discussed. Hence, if the parameters τm and m∞ and so forth were constants, we
would know
318
−t
m(t) = (m0 − m∞ ) e τm ) + m∞
−t
h(t) = (h0 − h∞ ) e τh ) + h∞
−t
n(t) = (n0 − n∞ ) e τn ) + n∞
with
1
τm =
αm + βm
αm
m∞ =
αm + βm
1
τh =
αh + βh
αh
h∞ =
αh + βh
1
τn =
αn + βn
αn
n∞ =
αn + βn
However, all of the coefficient functions, α and β for each variable required data fits as functions of
voltage. These were determined to be
V + 35.0
αm = −0.10
e−.1 (V +35.0) − 1.0
−(V +60.0
βm = 4.0 e 18.0
αh = 0.07 e−.05 (V +60.0) (17.9)

1.0
βh =
(1.0 + e−.1 (V +30.0) )
0.01 ∗ (V + 50.0
αn = − −.1(V +50.0)
(e − 1.0)
βn = 0.125 e−0.0125 (V +60.0
(17.10)
319
Of course these data fits were obtained at a certain temperature and assumed values for all the other
constants needed. These other parameters are given in the units below
voltage mV milli volts 10−3 Volts

current na nano amps 10−9 Amps
time ms milli seconds 10−3 Seconds
concentration mM milli moles 10−3 Moles
conductance µS micro Siemens 10−6 ohms−1
capacitance nF nano Fahrads 10−9 Fahrads
Our model of the membrane dynamics here thus consists of the following differential equations:
dm
τm = m∞ − m
dt
dh
τh = h∞ − h
dt
dn
τn = n∞ − n
dt
dV IM − IK − IN a − IL
=
dt CM
with initial conditions
m(0) = m∞ (V0 , 0)
h(0) = h∞ (V0 , 0)
n(0) = m∞ (V0 , 0)
V (0) = V0
We note that at equilibrium there is no current across the membrane. Hence, the sodium and potassium
currents are zero and the activation and inactivation variables should achieve their steady state values
which would be m∞ , h∞ and n∞ computed at the equilibrium membrane potential which is here
denoted by V0 .
320
17.4 The Hodgkin - Huxley Model Solution Under The Voltage
Clamp Protocol:
In this situation, we must solve Equation 17.7,
dVm 1
= (IK + IN a + IL − IE )
dt CM
1
= (gN a (V, t)(Vm − EK ) + gK (V, t)(Vm − EN a ) + gL (Vm − EL ) − IE )
CM

3
= M ax
gN M ax
a MN A (V, t) HN A (V, t) + gK HK 4 (V, t) + gL (Vm − EL ) − IE
using all the machinery of activation/ inactivation variables we have described.
17.4.1 Encoding The Dynamics:
Now these dynamics are more difficult to solve than you might think. The sequence of steps is this:
• Given the time t and voltage V compute
V + 35.0
αm = −0.10
e−.1 (V +35.0)
− 1.0
−(V +60.0)
βm = 4.0 e 18.0
αh = 0.07 e−.05 (V +60.0)

1.0
βh =
(1.0 + e−.1 (V +30.0)
0.01 ∗ (V + 50.0)
αn = − −.1(V +50.0)
(e − 1.0)
βn = 0.125 e−0.0125 (V +60.0)
• Then compute the τ and steady state activation and inactivation variables
1
τm =
αm + βm
321
αm
m∞ =
αm + βm
1
τh =
αh + βh
αh
h∞ =
αh + βh
1
τn =
αn + βn
αn
n∞ =
αn + βn
• Then compute the sodium and potassium potentials. In this model, this is easy as each is
set only once since the internal and external ion concentrations always stay the same and so
Nernst’s equation only has to used one time. Here we use the concentrations
[NA]o = 491.0
[NA]i = 50.0
[K]o = 20.11
[K]i = 400.0
These computations are also dependent on the temperature which is set to 9.3 degrees C.
• Next compute the conductances since we now know m(V, t), HN A (V, t) and n(V, t).
M ax 3
M ax
gK (V, t) = gK HK 4 (V, t)
M ax M ax
Now here we will need the maximum sodium and potassium conductances gN a and gK to
finish the computation. These values must be provided as data and in this model are not time
dependent. Here we use
322
M ax
gN a = 120.0
M ax
gK = 36.0
• Then compute the ionic currents:
IN a = gN A (V, t)(V (t) − EN A )
IK = gK (V, t)(V (t) − EK )
IL = gL (V, t)(V (t) − EL )
where we use
gL = 0.3
EL = −49.0
• Finally compute the total current
IT = IN A + IK + IL
• We can now compute the dynamics of our system at time t and voltage V : we let IM denote the
external current to our system which we must supply.
dV IM − IT
=
dt CM
323
dm m∞ − m
=
dt τm
dh h∞ − h
=
dt τh
dn n∞ − n
=
dt τn
where we use CM = 1.0.
The basic Hodgkin - Huxley model thus needs four independent variables which we place in a four
dimensional vector y which components assigned as follows:
 
 y[0] = V 
 
 
 y[1] = m 
 
y = 



 y[2] = h 
 
 
 
y[3] = n
We encode the dynamics calculated above into a four dimensional vector f whose components are
interpreted as follows:
 
IM − IT
 f [0] = CM 
 
 
 f [1] m∞ − m
 = τm


f= = 



 f [2] h∞ − h
 = τh


 
 
n∞ − n
f [3] = τn
which in terms of our vector y becomes
 
m∞ − y[1]
 f [1] = τm 
 
h∞ − y[2]
 
 f [2] = 

 τh 

n∞ − y[3]
 
f [3] = τn
324
So to summarize, at each time t and V , we need to calculate the four dimensional dynamics vector f
for use in our choice of ODE solver.
17.5 Computing the Solution:
As an example of what we might do to solve this kind of a problem, we note that this system can now
be written in vector form as
dy
= f (t, y)
dt
y(0) = y0
where we have found that
 
 V 
 
 
 m 
 
y = 

,

 h 
 
 
 
n
 
IM − IT

 CM 

 
 m∞ − m 
 τm 
f = 



 h∞ − h 

 τh 

 
n∞ − n
τn
with initial data
325
 
 V0 
 
 
 m 
 ∞ 
y0 = 



 h 
 ∞ 
 
 
n∞
The hardest part is to encode all of this in the vector form. The dynamic component f [0] is actually a
complicated function of m, h and n as determined by the encoding sequence we have previously dis-
cussed. Hence, the calculation of the dynamics vector f is not as simple as defining each component
of f as a functional expression.
17.6 Hodgkin - Huxley C++ Simulation Code:
We begin with a simple Hodgkin - Huxley giant squid axon simulation. The system to solve is encoded
in the following function:
17.6.1 function.c:
The giant squid axon system is encoded here for use in a standard Runga - Kutta - Fehlberg Order 5
method. We only use simple sodium and potassium gates here. The function prototype is as follows:
Listing 17.1: The Simple Hodgkin - Huxley Dynamics Prototype

# i n c l u d e "simulation.h"
/ ∗−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−
T h i s f u n c t i o n m o d e l s s i m p l e HH d y n a m i c s : Na and K g a t e s
5 only .
−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−∗ /
v o i d f u n c p ( d o u b l e t , DOUBLE VECTOR& y , DOUBLE VECTOR& f ,

DOUBLE VECTOR& p )
10 {
d o u b l e g NA bar = p[0];
double g K1 bar = p[1];
double g l e a k b a r = p [ 2 ] ;
d o u b l e E NA = p[3];
326
15 double E K = p[4];
double E L = p[5];
d o u b l e sum ;
d o u b l e I NA , I K1 ;
20 // units
/ ∗===============================================
T h i s i s t h e c l a s s i c Hodgkin H u x l e y Model .
voltage mV
current na
25 time ms
c o n c e n t r a t i o n mM
conductance micro Siemens
capacitance nF
===============================================∗ /
30 / / y vector assignments
/ ∗===============================================
y [0] = V
y [ 1 ] = m NA = = m
y [ 2 ] = h NA = = h
35 y [ 3 ] = m K1 = = n
===============================================∗ /
The inputs are time, t, the vector y which contains the state of the simulation model, f is the
dynamics force vector and p is a parameter vector which stores conveninent information. In this
simulation, p is defined as follows:
p[0] = g N A
p[1] = g K1
p[2] = g leak
p[3] = EN A
p[4] = EK
p[5] = EL
Next, we initialize variables:
Listing 17.2: Dynamics Initialization

d o u b l e g NA bar = p[0];
327

double g leak bar = p[2];
double E NA = p[3];
5 double E K = p[4];
double E L = p[5];
d o u b l e sum ;
d o u b l e I NA , I K1 ;
Then, we compute the current updates:
Sodium Current
Listing 17.3: Fast Sodium Current

/ ∗===============================================
Sodium C u r r e n t
===============================================∗ /
/ / a c t i v a t i o n p a r a m e t e r f o r I NA
5 d o u b l e alpha mNA ;
d o u b l e beta mNA ;
double m N A i n f i n i t y ;
d o u b l e t m NA ;
10 sum = y [ 0 ] + 3 5 . 0 ;
i f ( sum >0){
alpha mNA = −0.10∗ sum / ( exp ( −0.1∗ sum ) − 1 . 0 ) ;
}
else{
15 alpha mNA = −0.10∗ sum∗ exp ( 0 . 1 ∗ sum ) / ( 1 . 0 − exp ( 0 . 1 ∗ sum ) ) ;
}
sum = y [ 0 ] + 6 0 . 0 ;
beta mNA = 4 . 0 ∗ exp (−sum / 1 8 . 0 ) ;
m N A i n f i n i t y = alpha mNA / ( alpha mNA+beta mNA ) ;
20 t m NA = 1 . 0 / ( alpha mNA+beta mNA ) ;
f [1] = ( m N A i n f i n i t y − y [ 1 ] ) / t m NA ;
/ / i n a c t i v a t i o n p a r a m e t e r f o r I NA
d o u b l e alpha hNA ;
25 d o u b l e beta hNA ;
double h N A i n f i n i t y ;
d o u b l e t h NA ;
sum = y [ 0 ] + 6 0 . 0 ;
30 alpha hNA = 0 . 0 7 ∗ exp (−sum / 2 0 . 0 ) ;
sum = y [ 0 ] + 3 0 . 0 ;
i f ( sum >0){
beta hNA = 1 . 0 / ( 1 . 0 + exp (−sum / 1 0 . 0 ) ) ;
}
328
35 else{
beta hNA = exp ( sum / 1 0 . 0 ) / ( exp ( sum / 1 0 . 0 ) + 1 . 0 ) ;
}
h N A i n f i n i t y = alpha hNA / ( alpha hNA + beta hNA ) ;
t h NA = 1 . 0 / ( alpha hNA + beta hNA ) ;
40 f [2] = ( h N A i n f i n i t y − y [ 2 ] ) / t h NA ;
I NA = g NA bar ∗ ( y [0] −E NA ) ∗ y [ 1 ] ∗ y [ 1 ] ∗ y [ 1 ] ∗ y [ 2 ] ;
Potassium Current
Listing 17.4: Transient, Outward Potassium Current

/ ∗===============================================
Potassium Current
===============================================∗ /
/ / a c t i v a t i o n parameter for I K
5 double alpha m K1 ;
double beta m K1 ;
d o u b l e t m K1 ;
double m K 1 i n f i n i t y ;
10 sum = y [ 0 ] + 5 0 . 0 ;
i f ( sum >0){
a l p h a m K 1 = − 0 . 0 1 ∗ sum / ( exp (−sum / 1 0 . 0 ) − 1 . 0 ) ;
}
else{
15 a l p h a m K 1 = − 0 . 0 1 ∗ sum∗ exp ( sum / 1 0 . 0 ) / ( 1 . 0 − exp ( sum / 1 0 . 0 ) ) ;
}
sum = y [ 0 ] + 6 0 . 0 ;
b e t a m K 1 = 0 . 1 2 5 ∗ exp ( −0.0125∗ sum ) ;
m K 1 i n f i n i t y = alpha m K1 / ( alpha m K1+beta m K1 ) ;
20 t m K1 = 1 . 0 / ( alpha m K1+beta m K1 ) ;
f [3] = ( m K 1 i n f i n i t y − y [ 3 ] ) / t m K1 ;
I K1 = g K 1 b a r ∗ ( y [0] − E K ) ∗ y [ 3 ] ∗ y [ 3 ] ∗ y [ 3 ] ∗ y [ 3 ] ;
Leakage Current
Listing 17.5: Leakage Current

/ ∗========================================================
leakage current
========================================================∗ /
d o u b l e I l e a k = g l e a k b a r ∗ ( y [0] − E L ) ;
329
Figure 17.5: The Applied Synaptic Pulse:
External Current
We apply external current in a series of four low level excitations as
(t−0.2)2 (t−0.3)2 (t−0.4)2 (t−0.5)2

IE (t) = 1.0e− 0.1 + 1.0e− 0.1 + 1.0e− 0.1 + 7.0e− 0.4 +
which we can see in Figure 17.5 injects a modest amount of current over approximately 2
seconds.
This is coded in C++ as follows within the module function.c.
Listing 17.6: Applied Synaptic Current

double external current 1 ;
5 double I E;
s t a t i c double d e l t a t 1 = 0 . 1 ;
s t a t i c double t s t a r t 1 = 0 . 2 ;
s t a t i c double i n j e c t i o n 1 = 1 . 0 ;
10
330
15 s t a t i c double d e l t a t 3 = 0 . 1 ;
20 s t a t i c double t s t a r t 4 = 0 . 5 ;
double sqdt 1 = −( t−t start 1 )∗( t−t start 1 )/ delta t 1 ;

25 double sqdt 3 = −( t−t start 3 )∗( t−t start 3 )/ delta t 3 ;
external current 1 = injection 1 ∗ exp ( s q d t 1 );

30 external current 3 = injection 3 ∗ exp ( s q d t 3 );
I E = external current 1 + external current 2

+ external current 3 + external current 4 ;
Computing The Voltage Update
Listing 17.7: Voltage Update

s t a t i c double C N = 1 . 0 ;
f [ 0 ] = ( I E − I NA − I K1 − I l e a k ) / C N ;
17.6.2 rest.c:
The initial conditions for the activation and inactivation variables for this model should be calculated
carefully. When the excitable nerve cell is at equilibrium, with no external current applied, there is no
net current flow across the membrane. At this point, the voltage across the membrane should be the
applied voltage EM . Therefore,
0 = IT
= IN A + IK1 + IL
= g N A (EM − EN A ) (m∞ )3 h∞ + g K (EM − EK ) (n∞ )4 + g L (EM − EL )
331
The two parameters, gL and EL , are used to take into account whatever ionic currents flow across the
membrane that are not explicitly modeled. We know this model does not deal with various pumps, a
variety of potassium gates, calcium gates and so forth. We also know there should be no activity at
equilibrium in the absence of an external current. However, it is difficult to choose these parameters.
So first, solve to the leakage parameters in terms of the rest of the variables. Also, we can see that
the activation and inactivation variables for each gate at equilibrium will take on the values that are
calculated using the voltage EM . We can use the formulae given in the Hodgkin - Huxley dynamics
to compute mr ≡ m∞ (EM ), hr ≡ h∞ (EM ) and nr ≡ n∞ (EM ) and Then, we can calculate the
equilibrium currents
INr A = g N A (EM − EN A ) (mr )3 hr
IK = g K (EM − EK ) (nr )4
Thus, we see we must choose g L and EL so that
g L (EL − EM ) = INr A + IK
r
or
r
g L (EL − EM ) = INr A + IK
If we choose to fix EL , we can solve for the leakage conductance
INr A + IK
r
gL =
EL − EM
We do this in a startup function rest.c. This code is almost identical to the code we see in function.c.
332
The function prototype is
Listing 17.8: Calculating Hodgkin - Huxley Initial Conditions

v o i d r e s t ( d o u b l e E M , DOUBLE VECTOR& p , DOUBLE VECTOR& q )

{}
The inputs are the chosen initial membrane voltage, EM , the previously defined set of simulation
parameters stored in p, with components defined by
p[0] = g N A
p[1] = g K
p[2] = g leak
p[3] = EN A
p[4] = EK
p[5] = EL
and a vectors q that will be calculated by the routine which will contain the initial values we should
use for the simulation; this has the components
q[0] = m∞
q[1] = hi nf ty
q[2] = ni nf ty
Finally,the routine returns the value of EL . The first part of the code is some initialization.
Listing 17.9: Initializing The Rest Code

d o u b l e sum ;
333
double g NA bar = p[0];

5 double g leak bar = p[2];
double E NA = p[3];
double E K = p[4];
double E L = p[5];
Compute INr A :
Listing 17.10: Computing the Sodium Equilibrium Current

/ ∗===============================================
E q u i l i b r i u m Sodium C u r r e n t
===============================================∗ /
/ / a c t i v a t i o n p a r a m e t e r f o r I NA
5 d o u b l e alpha mNA ;
double m N A i n f i n i t y ;
sum = E M + 3 5 . 0 ;
10 i f ( sum >0){
}
else{
alpha mNA = −0.10∗ sum∗ exp ( 0 . 1 ∗ sum ) / ( 1 . 0 − exp ( 0 . 1 ∗ sum ) ) ;
15 }
sum = E M + 6 0 . 0 ;
beta mNA = 4 . 0 ∗ exp (−sum / 1 8 . 0 ) ;
m NA infinity = alpha mNA / ( alpha mNA+beta mNA ) ;
20 / / i n a c t i v a t i o n p a r a m e t e r f o r I NA
d o u b l e beta hNA ;
double h N A i n f i n i t y ;
25 sum = E M + 6 0 . 0 ;
alpha hNA = 0 . 0 7 ∗ exp (−sum / 2 0 . 0 ) ;
sum = E M + 3 0 . 0 ;
i f ( sum >0){
beta hNA = 1 . 0 / ( 1 . 0 + exp (−sum / 1 0 . 0 ) ) ;
30 }
else{
}
h NA infinity = alpha hNA / ( alpha hNA + beta hNA ) ;
35
d o u b l e I NA = g NA bar ∗ ( E M−E NA )
∗ m NA infinity ∗ m NA infinity
334
∗ m NA infinity ∗ h NA infinity ;
Compute IK1 :
Listing 17.11: Computing The Potassium Equilibrium Current

/ ∗===============================================
Equilibrium Potassium Current
===============================================∗ /
5 double alpha m K1 ;
double beta m K1 ;
double m K 1 i n f i n i t y ;
10 sum = E M + 5 0 . 0 ;
i f ( sum >0){
a l p h a m K 1 = − 0 . 0 1 ∗ sum / ( exp (−sum / 1 0 . 0 ) − 1 . 0 ) ;
}
else{
15 a l p h a m K 1 = − 0 . 0 1 ∗ sum∗ exp ( sum / 1 0 . 0 ) / ( 1 . 0 − exp ( sum / 1 0 . 0 ) ) ;
}
sum = E M + 6 0 . 0 ;
b e t a m K 1 = 0 . 1 2 5 ∗ exp ( −0.0125∗ sum ) ;
m K 1 i n f i n i t y = alpha m K1 / ( alpha m K1+beta m K1 ) ;
20
d o u b l e I K1 = g K 1 b a r ∗ ( E M−E K ) ∗ m K 1 i n f i n i t y ∗ m K 1 i n f i n i t y
∗ m K1 infinity ∗ m K1 infinity ;
Compute The Leakage Conductance:
Listing 17.12: Computing The Leakage Conductance

sum = I NA + I K1 ;
g l e a k b a r = −sum / ( E M−E L ) ;
p [2] = g leak bar ;
Compute Initial Variables;

Note that the values stored in q will not change unless the following parameters are altered:
• inner and outer ion concentrations as this will change the ion battery voltages
• temperature as this will also change the ion battery voltages
335
Changing maximum sodium and potassium conductances will necessitate a change in the leak-
age conductance to maintain zero current at equilibrium but will not alter the starting parameters
stored in q.
Listing 17.13: Computing The Initial Variables

q [ 0 ] = m NA infinity ;
q [1] = h NA infinity ;
q [2] = m K1 infinity ;
17.6.3 run plot.c:
The initialization of the simulation itself is handled by the callback run plot.c which sets the param-
eters for the ODE solver, the initial conditions for the ion concentrations and so forth. We begin by
initializing our state vectors, computing battery voltages and so forth.
Listing 17.14: Some Initial Calculations

v o i d r u n p l o t ( Widget w, X t P o i n t e r c l i e n t d a t a , X t P o i n t e r c a l l d a t a )
{
5 XmPushButtonCallbackStruct ∗ P = ( XmPushButtonCallbackStruct ∗ ) c a l l d a t a ;
application data ∗T = ( application data ∗) c l i e n t d a t a ;
int i ;
10 int size = 4;
double t o l , t i n i t , tend , h i n i t ;
/ ∗======================================
A l l o c a t e memory f o r s t a t e v a r i a b l e s
15 ======================================∗ /
DOUBLE VECTOR y i n i t ( s i z e ) ;
DOUBLE VECTOR y ( s i z e ) ;
double C = 6 . 3 ; / / o l d was 9 . 3
20 / ∗======================================
A l l o c a t e memory f o r d y n a m i c p a r a m e t e r s
p [ 0 ] g NA bar
p [ 1 ] g K1 bar
p [2] g leak bar
25 p [ 3 ] E NA
p[4] E K
p[5] E L
336
q [ 0 ] = m NA ( 0 ) ;
30 q [ 1 ] = h NA ( 0 ) ;
q [ 2 ] = m K1 ( 0 ) ;
======================================∗ /
DOUBLE VECTOR p ( 6 ) ;
35 DOUBLE VECTOR q ( 3 ) ;
/ ∗−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−
Koch v a l u e s
−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−∗ /
40 d o u b l e g NA bar = 120.0;
double g K1 bar = 36.0;
double g l e a k b a r = 0.3;
double NA O = 491.0;
45 double NA I = 50.0;
double KO = 20.11;
double K I = 400.0;
double R = 8.31; / / Rydberg ’ s C o n s t a n t

50 double DegK = 2 7 6 . 0 + C ; / / Kelvin Temperature ; use C degrees C e l s i u s
double F = 9.649 e +4; / / Faraday ’ s c o n s t a n t
double RTF = R∗DegK / F∗1 e + 3 ;
d o u b l e E NA ;
55 E NA = RTF∗ l o g ( NA O / NA I ) ;
double E K ;
E K = RTF∗ l o g ( K O / K I ) ;
double E M = − 6 5 . 9 ;
60 double E L = − 4 9 . 0 ;
p[0] = g NA bar ;
p[1] = g K1 bar ;
p[2] = g leak bar ;
65 p[3] = E NA ;
p[4] = E K;
p[5] = E L;
We then use these values to compute the necessary leakage conductance by calling the rest() function.
This also calculates the proper initialization values for the state vector. We also list the plot types so
we won’t forget! We also need minimum and maximum values for the range of each variable. Here
we enter values that are not necessarily correct. We actually do most of our data plotting using Python
in another set of code and we don’t often graph anything other than voltage to the X Window.
337
Listing 17.15: Computing The Leakage Conductance
r e s t (E M, p , q ) ;
g leak bar = p [2];
5 cout << "E_NA = " << E NA << e n d l ;

cout << "E_K = " << E K << e n d l ;
cout << "E_M = " << E M << e n d l ;
cout << "E_L = " << E L << e n d l ;
cout << "g_leak_bar = " << g l e a k b a r << e n d l ;
10
/ ∗======================================
S e t up i n i t i a l c o n d i t i o n s
======================================∗ /
T−> i n i t i a l = new DOUBLE VECTOR( s i z e ) ;
15 DOUBLE VECTOR& INIT = ∗ ( T−> i n i t i a l ) ;
INIT [ 0 ] = E M;
INIT [ 1 ] = q[0];
INIT [ 2 ] = q[1];
20 INIT [ 3 ] = q[2];
/ / y vector assignments
/ ∗===============================================
y [0] = V
25 y [ 1 ] = m NA
y [ 2 ] = h NA
y [ 3 ] = m K1
p l o t t y p e = 0 == > y [ 0 ] range [ −80 ,100]

30 p l o t t y p e = 1 == > y [ 1 ] range [ 0 , 1 ]
p l o t t y p e = 2 == > y [ 2 ] range [ 0 , 1 ]
p l o t t y p e = 3 == > y [ 3 ] range [ 0 , 1 ]
p l o t t y p e = 4 == > alpha m NA range [ 0 , 5 0 ]
p l o t t y p e = 5 == > beta m NA range [ 0 , 5 0 ]
35 p l o t t y p e = 6 == > a l p h a h N A range [ 0 , 5 0 ]
p l o t t y p e = 7 == > b e t a h N A range [ 0 , 5 0 ]
p l o t t y p e = 8 == > a l p h a m K 1 range [ 0 , 5 0 ]
p l o t t y p e = 9 == > b e t a m K 1 range [ 0 , 5 0 ]
p l o t t y p e = 1 0 == > m N A i n f i n i t y r a n g e [ 0 , 1 ]
40 p l o t t y p e = 1 1 == > h N A i n f i n i t y r a n g e [ 0 , 1 ]
p l o t t y p e = 1 2 == > m K 1 i n f i n i t y r a n g e [ 0 , 1 ]
p l o t t y p e = 1 3 == > t m NA range [ 0 , 1 ]
p l o t t y p e = 1 4 == > t h N A range [ 0 , 1 ]
p l o t t y p e = 1 5 == > t m K 1 range [ 0 , 1 ]
45 p l o t t y p e = 1 6 == > I N a range [ 0 , 1 ]
p l o t t y p e = 1 7 == > I K range [ 0 , 1 ]
p l o t t y p e = 1 8 == > I L range [ 0 , 1 ]
===============================================∗ /
DOUBLE VECTOR Low Range ( 1 9 ) ;
338
50 DOUBLE VECTOR High Range ( 1 9 ) ;

Low Range [ 0 ] = −80 .0;
High Range [ 0 ] = 1 0 0 . 0 ;
Low Range [ 1 ] = 0.0;
High Range [ 1 ] = 1.0;
55 Low Range [ 2 ] = 0.0;
High Range [ 2 ] = 1.0;
Low Range [ 3 ] = 0.0;
High Range [ 3 ] = 1.0;
Low Range [ 4 ] = 0.0;
60 High Range [ 4 ] = 50.0;
Low Range [ 5 ] = 0.0;
High Range [ 5 ] = 50.0;
Low Range [ 6 ] = 0.0;
High Range [ 6 ] = 50.0;
65 Low Range [ 7 ] = 0.0;
High Range [ 7 ] = 50.0;
Low Range [ 8 ] = 0.0;
High Range [ 8 ] = 50.0;
Low Range [ 9 ] = 0.0;
70 High Range [ 9 ] = 50.0;
Low Range [ 1 0 ] = 0.0;
High Range [ 1 0 ] = 1.0;
Low Range [ 1 1 ] = 0.0;
High Range [ 1 1 ] = 1.0;
75 Low Range [ 1 2 ] = 0.0;
High Range [ 1 2 ] = 1.0;
Low Range [ 1 3 ] = 0.0;
High Range [ 1 3 ] = 1.0;
Low Range [ 1 4 ] = 0.0;
80 High Range [ 1 4 ] = 1.0;
Low Range [ 1 5 ] = 0.0;
High Range [ 1 5 ] = 1.0;
Low Range [ 1 6 ] = 0.0;
High Range [ 1 6 ] = 1.0;
85 Low Range [ 1 7 ] = 0.0;
High Range [ 1 7 ] = 1.0;
Low Range [ 1 8 ] = 0.0;
High Range [ 1 8 ] = 1.0;
Finally, the last part of the code calls the ode solution engine and plotting code contained in the
function oderkf5 plot().
Listing 17.16: Computing A Solution

int plot type ;
/ ∗========================================
S e t up p a r a m e t e r s f o r ode i n t e g r a t i o n
========================================∗ /
339
5 plot type = 0;
d o u b l e ymin = Low Range [ p l o t t y p e ] ; ;
d o u b l e ymax = High Range [ p l o t t y p e ] ; ;
hinit = 1 . 0 e −8;
10 tinit = 0.00;
tend = 25.0;
tol = 1 . 0 e −12;
T−>PLOT−>p l o t t y p e = p l o t t y p e ;
T−>PLOT−>x minimum = t i n i t ;
15 T−>PLOT−>x maximum = t e n d ;
T−>PLOT−>y minimum = ymin ;
T−>PLOT−>y maximum = ymax ;
y i n i t = INIT ;
y = INIT ;
20 c o u t << "yinit = " << y i n i t << e n d l ;
c o u t << "parameters = " << p << e n d l << e n d l ;
o d e r k f 5 p l o t ( y i n i t , y , p , t o l , t i n i t , tend , h i n i t , T ,w) ;
}
17.6.4 rkf5 plot.c:
The actual call to the ODE solver is handled by the utility function rkf5 plot.c which splits the
integration interval into manageable chunks for plotting purposes. We also need to compute the
values of our simulation variables after each data run. We do this in the auxiliary function gates()
whose code is given below:
Listing 17.17: Computing The Simulation Variables

v o i d g a t e s (DOUBLE VECTOR& y , DOUBLE VECTOR& G a t e s ,

DOUBLE VECTOR& p )
5 {
d o u b l e sum ;
double Voltage = y [ 0 ] ;
d o u b l e m NA = y[1];
d o u b l e h NA = y[2];
10 d o u b l e m K1 = y[3];
double g NA bar = p[0];

double g leak bar = p[2];
15 double E NA = p[3];
double E K = p[4];
340
double E L = p[5];
/ ∗===================================================
20 G a t e s [ 0 ] = alpha m NA ;
G a t e s [ 1 ] = beta m NA ;
Gates [ 2 ] = alpha h NA ;
Gates [ 3 ] = beta h NA ;
Gates [ 4 ] = alpha m K1 ;
25 Gates [ 5 ] = beta m K1 ;
Gates [ 6 ] = m N A i n f i n i t y ;
Gates [ 7 ] = h N A i n f i n i t y ;
Gates [ 8 ] = m K 1 i n f i n i t y ;
G a t e s [ 9 ] = t m NA ;
30 Gates [ 1 0 ] = t h NA ;
Gates [ 1 1 ] = t m K1 ;
G a t e s [ 1 2 ] = I NA ;
Gates [ 1 3 ] = I K1 ;
Gates [ 1 4 ] = I L ;
35 ===================================================∗ /
/ ∗===============================================
Sodium C u r r e n t
===============================================∗ /
40 / / a c t i v a t i o n p a r a m e t e r f o r I NA
d o u b l e alpha mNA ;
d o u b l e m N A i n f i n i t y , t m NA ;
45 sum = V o l t a g e + 3 5 . 0 ;
i f ( sum >0){
}
else{
50 alpha mNA = −0.10∗ sum∗ exp ( 0 . 1 ∗ sum ) / ( 1 . 0 − exp ( 0 . 1 ∗ sum ) ) ;
}
sum = V o l t a g e + 6 0 . 0 ;
beta mNA = 4 . 0 ∗ exp (−sum / 1 8 . 0 ) ;
m N A i n f i n i t y = alpha mNA / ( alpha mNA+beta mNA ) ;
55 t m NA = 1 . 0 / ( alpha mNA+beta mNA ) ;
/ / i n a c t i v a t i o n p a r a m e t e r f o r I NA
d o u b l e beta hNA ;
60 d o u b l e h N A i n f i n i t y , t h NA ;
sum = V o l t a g e + 6 0 . 0 ;
alpha hNA = 0 . 0 7 ∗ exp (−sum / 2 0 . 0 ) ;
sum = V o l t a g e + 3 0 . 0 ;
65 i f ( sum >0){
beta hNA = 1 . 0 / ( 1 . 0 + exp (−sum / 1 0 . 0 ) ) ;
341
}
else{
70 }
t h NA = 1 . 0 / ( alpha hNA + beta hNA ) ;
d o u b l e I NA = g NA bar ∗ ( V o l t a g e −E NA )
75 ∗m NA∗m NA
∗m NA∗h NA ;
/ ∗===============================================
Potassium Current
80 ===============================================∗ /
d o u b l e alpha mK1 ;
d o u b l e beta mK1 ;
85 double m K 1 i n f i n i t y ;
sum = V o l t a g e + 5 0 . 0 ;
i f ( sum >0){
alpha mK1 = − 0 . 0 1 ∗ sum / ( exp (−sum / 1 0 . 0 ) − 1 . 0 ) ;
90 }
else{
alpha mK1 = − 0 . 0 1 ∗ sum∗ exp ( sum / 1 0 . 0 ) / ( 1 . 0 − exp ( sum / 1 0 . 0 ) ) ;
}
sum = V o l t a g e + 6 0 . 0 ;
95 beta mK1 = 0 . 1 2 5 ∗ exp ( −0.0125∗ sum ) ;
m K 1 i n f i n i t y = alpha mK1 / ( alpha mK1 + beta mK1 ) ;
t m K1 = 1 . 0 / ( alpha mK1 + beta mK1 ) ;
d o u b l e I K1 = g K 1 b a r ∗ ( V o l t a g e −E K ) ∗ m K1∗m K1
∗m K1∗m K1 ;
100 d o u b l e I L = g l e a k b a r ∗ ( V o l t a g e −E L ) ;
Gates [0] = alpha mNA ;

Gates [1] = beta mNA ;
Gates [2] = alpha hNA ;
105 Gates [3] = beta hNA ;
Gates [4] = alpha mK1 ;
Gates [5] = beta mK1 ;
Gates [6] = m NA infinity ;
Gates [7] = h NA infinity ;
110 Gates [8] = m K1 infinity ;
Gates [9] = t m NA ;
Gates [10] = t h NA ;
Gates [11] = t m K1 ;
Gates [12] = I NA ;
115 Gates [13] = I K1 ;
Gates [14] = I L;
342
For graphing needs, we want to generate a sequence of N pairs {(ti , yi ) : 0 ≤ i < N } with the
time coordinates uniformly spaced between the initial and final times for our simulation run. Since
we are using a variable step ODE solver, it is difficult to force time steps to occur at the knots we
choose (although not impossible). For our purposes, we have chosen the somewhat inefficient method
of choosing a uniform time mesh first and then calling the ODE solver on each interval of the form
[ti , ti + H] where H is our uniform time step. The ODE code is already setup to choose the time step
so as to terminate at whatever final time is chosen. Hence, we can generate the uniform mesh data
we desire using this method. The initial setup of the uniform mesh is given below. Here, we want 40
time points per millisecond time unit. Since these simulations are over 25 milliseconds, this will give
us 1000 data pairs for each variable we are interested in the simulation. The code below saves the
results of the simulation for 20 different variables. The variables for voltage, m, h and n are computed
directly by the ODE solver, but all the other variables listed below must be computed by the gates()
function. Thus, we generate a lot of data for each run! The constant FREQ sets how often we ouput
computational results to a xterm window. The variables of the simulation are indexed by a counter
that ranges from 0 to 18. The variable plot type stores the index of the simulation variable we wish
to see plotted in our X window.
Listing 17.18: Organizing The ODE Solver

# i n c l u d e < i o s t r e a m . h>
/ ∗==========================================================∗ /
/∗ ∗/
5 / ∗ Runga−F e h l b e r g o r d e r 5 method f o r p l o t t i n g ∗/
/∗ ∗/
/∗ y i n i t = initial state ∗/
/∗ y = calculated state ∗/
/∗ u = c o n t r o l parameter ∗/
10 /∗ t i n i t = initial t ∗/
/∗ tend = final t ∗/
/∗ t o l = t o l e r a n c e f o r s t e p s i z e changing ∗/
/∗ h i n i t = i n i t i a l step size ∗/
/ ∗==========================================================∗ /
15 v o i d o d e r k f 5 p l o t (DOUBLE VECTOR& y i n i t ,
DOUBLE VECTOR& y , DOUBLE VECTOR& p , d o u b l e t o l ,
double t i n i t , double tend , double h i n i t ,
343
application data ∗T,

Widget w)
20 {
/ / open f i l e s f o r p l o t d a t a
ofstream fd2 ;
f d 2 . open ( "classicalhh" , i o s : : app ) ;
DOUBLE VECTOR GATES ( 1 5 ) ;
25 / ∗========================================
We m i g h t want t o p l o t a l l o f t h e v a r i a b l e s
i n o u r s i m u l a t i o n . Hence , we c a l c u l a t e a l l
o f them i n t h e g a t e s ( ) f u n c t i o n .
The c o m p o n e n t s o f t h e G a t e s v e c t o r c o r r e s p o n d
30 t o s i m u l a t i o n v a r i a b l e s as f o l l o w s :
G a t e s [ 0 ] = alpha m NA ;
G a t e s [ 1 ] = beta m NA ;
Gates [ 2 ] = alpha h NA ;
35 Gates [ 3 ] = beta h NA ;
Gates [ 4 ] = alpha m K1 ;
Gates [ 5 ] = beta m K1 ;
Gates [ 6 ] = m N A i n f i n i t y ;
Gates [ 7 ] = h N A i n f i n i t y ;
40 Gates [ 8 ] = m K 1 i n f i n i t y ;
G a t e s [ 9 ] = t m NA ;
Gates [ 1 0 ] = t h NA ;
Gates [ 1 1 ] = t m K1 ;
G a t e s [ 1 2 ] = I NA ;
45 Gates [ 1 3 ] = I K1 ;
Gates [ 1 4 ] = I L ;
============================================∗ /
i n t POINTS PER UNIT = 4 0 ;
i n t NUMBER PLOT POINTS = t e n d ∗POINTS PER UNIT ;
50 f l o a t HPLOT = ( t e n d − t i n i t ) / ( f l o a t ) NUMBER PLOT POINTS ;
double t f i n a l ;
int i , j , k ;
p l o t d a t a ∗ PLOT = ( p l o t d a t a ∗ ) ( T−>POP−>O u t s i d e D a t a ) ;
i n t p l o t t y p e = PLOT−>p l o t t y p e ;
55 i n t FREQ = 2 0 0 ;
}
Next, we initialize the plot, write the maximum sodium, potassium and leakage conductances we are
using for this simulation to our data file. We then compute all of the simulation variables using the
gates() function and write them to the file also.
Listing 17.19: Initializing The Data File

PLOT−>d r a w a x i s = 1 ;
t f i n a l = t i n i t + HPLOT ;
344
DOUBLE VECTOR y0 = y i n i t ;
g a t e s ( y [ 0 ] , GATES , p ) ;
5 PLOT−> f i r s t t i m e = t i n i t ;
i f (0<= p l o t t y p e && p l o t t y p e <=3){
PLOT−> f i r s t o r d i n a t e = y [ p l o t t y p e ] ;
}
e l s e i f (4<= p l o t t y p e && p l o t t y p e <=18){
10 PLOT−> f i r s t o r d i n a t e = GATES[ p l o t t y p e − 4 ] ;
}
/ / write ion conductances to top of f i l e for reference .
f d 2 << "G " << p [ 0 ] << " "
<< p [ 1 ] << " "
15 << p [ 2 ] << e n d l ;
f d 2 << t i n i t << " " << y [ 0 ]
<< " " << y [ 1 ]
<< " " << y [ 2 ]
<< " " << y [ 3 ]
20 << " " << GATES [ 0 ]
<< " " << GATES [ 1 ]
<< " " << GATES [ 2 ]
<< " " << GATES [ 3 ]
<< " " << GATES [ 4 ]
25 << " " << GATES [ 5 ]
<< " " << GATES [ 6 ]
<< " " << GATES [ 7 ]
<< " " << GATES [ 8 ]
<< " " << GATES [ 9 ]
30 << " " << GATES [ 1 0 ]
<< " " << GATES [ 1 1 ]
<< " " << GATES [ 1 2 ]
<< " " << GATES [ 1 3 ]
<< " " << GATES[14] < < e n d l ;
Then, we compute the solution at each mesh point via a standard for loop: some of the busy nature
of the code comes from the fact that our choice of plot type determines whether we can use variables
directly from the ODE solver (indices 0 to 3) or whether they come from the gates() function. We
then plot the initial and final pair of data from the computation at each mesh point. This shows up as
a straight line in the picture that is being built in the X window interface.
Listing 17.20: Computing The Solution

f o r ( i n t c o u n t = 0 ; c o u n t <NUMBER PLOT POINTS ; + + c o u n t ) {
int display counter = 1;
int plot counter = 1;
5 / / i n t e g r a t e from t i n i t t o t f i n a l
o d e r k f 5 p a r o b j e c t s ( y0 , y , p , t o l , t i n i t , t f i n a l , h i n i t ) ;
g a t e s ( y [ 0 ] , GATES , p ) ;
i f ( c o u n t%FREQ = = 0 | | c o u n t < 5 ) {
i f (0<= p l o t t y p e && p l o t t y p e <=3){
345
10 c o u t << "(t,y[" << p l o t t y p e << "]) = " << t f i n a l

<< "," << y [ p l o t t y p e ] < < e n d l ;
}
e l s e i f (4<= p l o t t y p e && p l o t t y p e <=18){
c o u t << "(t,GATES[" << p l o t t y p e −4 << "]) = " << t f i n a l
15 << "," << GATES[ p l o t t y p e −4] < < e n d l ;
}
}
PLOT−>s e c o n d t i m e = t f i n a l ;
20 i f (0<= p l o t t y p e && p l o t t y p e <=4){
PLOT−>s e c o n d o r d i n a t e = y [ p l o t t y p e ] ;
}
e l s e i f (5<= p l o t t y p e && p l o t t y p e <17){
PLOT−>s e c o n d o r d i n a t e = GATES[ p l o t t y p e − 5 ] ;
25 }
f d 2 << t f i n a l << " " << y [ 0 ]
<< " " << y [ 1 ]
<< " " << y [ 2 ]
<< " " << y [ 3 ]
30 << " " << GATES [ 0 ]
<< " " << GATES [ 1 ]
<< " " << GATES [ 2 ]
<< " " << GATES [ 3 ]
<< " " << GATES [ 4 ]
35 << " " << GATES [ 5 ]
<< " " << GATES [ 6 ]
<< " " << GATES [ 7 ]
<< " " << GATES [ 8 ]
<< " " << GATES [ 9 ]
40 << " " << GATES [ 1 0 ]
<< " " << GATES [ 1 1 ]
<< " " << GATES [ 1 2 ]
<< " " << GATES [ 1 3 ]
<< " " << GATES[14] < < e n d l ;
45 T−>POP−>Image (w, T−>POP ) ;
PLOT−>d r a w a x i s = 0 ;
PLOT−> f i r s t t i m e = PLOT−>s e c o n d t i m e ;
PLOT−> f i r s t o r d i n a t e = PLOT−>s e c o n d o r d i n a t e ;
// reset yinit
50 y0 = y ;
tinit = tfinal ;
t f i n a l + = HPLOT ;
} / / p l o t p o i n t s loop
fd2 . c l o s e ( ) ;
346
17.6.5 C++ Code: The Run-Time Code:
The simulation code is controlled by editing the files run plot.c and rkf5 plot.c to choose variables
to plot and so forth. Then, we recompile the executible using standard unix make tools. Typically, we
manage all of this with a unix Makefile: here is the one we use for this simulation:
Listing 17.21: The Hodgkin - Huxley Makefile

#−−−−−−−−−−−−−−−−−−−−−−−−− #
# X / Motif Paths #
#−−−−−−−−−−−−−−−−−−−−−−−−− #
MOTIFLIB = / u s r / X11R6 / l i b
5 XLIB = / u s r / X11R6 / l i b
#−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−− #
# Define X l i b r a r i e s location #
#−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−#
XLIBS = −lXm −lXp −lXpm −lXaw − l X t −lXmu − l X e x t − lX11
10 #−−−−−−−−−−−−−−−−−−−−−−−−−−−− #
# Define X include d i r e c t o r i e s #
#−−−−−−−−−−−−−−−−−−−−−−−−−−−− #
XINC = / u s r / X11R6 / i n c l u d e
MOTIFINC = / u s r / X11R6 / i n c l u d e
15 XINCLUDES = − I $ ( XINC) − I $ ( MOTIFINC )
#
MYMAKE = MakeApp
#
#−−−−−−−−−−−−−−−−−−−−−−−−−− #
20 # paths for t h i s simulation #
#−−−−−−−−−−−−−−−−−−−−−−−−−− #
BASE PATH = / home / p e t e r s j / ProgramsApp
SIM PATH = $ ( BASE PATH ) / C l a s s i c H H
#
25 MAIN LIBRARY PATH = / home / p e t e r s j / p r o g r a m s / J i m L i b s
MAIN INCLUDE PATH = / home / p e t e r s j / p r o g r a m s / J i m I n c l u d e s
INCLUDE PATH APP = $ ( BASE PATH ) / s i m o d e
INCLUDES = $ ( XINCLUDES) − I $ ( MAIN INCLUDE PATH ) \
−I $ ( INCLUDE PATH XGRAPH) − I $ ( INCLUDE PATH APP )
30 #
LIBRARY FLAGS SOURCES = − L$ ( MAIN LIBRARY PATH )
LIBRARY PATH X = $ ( XLIB )
LIBRARY PATH MOTIF = $ ( MOTIFLIB )
LIBRARY FLAGS SOURCES = − L$ ( MAIN LIBRARY PATH ) \
35 −L$ ( LIBRARY PATH MOTIF) − L$ ( LIBRARY PATH X )
SUNLIBS = − l l − l g e n
LIBS = −lm
SHAPE LIBS = − l b o x − l s h a p e
40 VECTOR LIBS = − l r k f 5 p a r o b j e c t s − l d o u b l e v e c 2 − l d o u b l e v e c 1 − l i n t v e c 2 − l i n t v e c 1
347
SIMLIBS = $ ( VECTOR LIBS ) $ ( SHAPE LIBS )

#
# −−−−−−−−−−− #
# Definitions #
45 # −−−−−−−−−−− #
DEFINES =
CC = g++
COMPILE FLAGS LINK = − g $ ( DEFINES ) $ ( INCLUDES )
COMPILE FLAGS SOURCES = − c −g $ ( DEFINES ) $ ( INCLUDES )
50 #
RANLIB = t o u c h
# −−−−−−−−−−−−− #
# Define t a r g e t #
# −−−−−−−−−−−−− #
55 TARGET = ode
OBJECTS = s e t t o x i n s i g n a t u r e . o \
set HH vector . o \
alpha beta . o \
current . o \
60 sim . o \
popupdrawExposeCB . o \
popupdrawResizeCB . o \
setxcolor . o \
find named color . o \
65 update color . o \
force update . o \
popupquitCB . o \
graph color . o \
axis color .o \
70 check points . o \
rkf5 plot .o \
function . o \
external force .o \
run plot . o \
75 set plot .o \
handle button release .o \
imagepopupplot . o \
set popupplot . o \
imagepopupcolor . o \
80 set axiscolor .o \
set graphcolor . o \
set active .o \
expose . o \
input . o \
85 resize .o \
quit application .o \
image . o \
r e s t . o\
g a t e s . o\
90 toxin . o
348
SOURCES = $ ( OBJECTS : . o = . c )
progs :
@make $ (TARGET) − f $ (MYMAKE)
95
$ (TARGET ) : $ ( OBJECTS ) s i m u l a t i o n . h
@echo
@echo C r e a t i n g t h e E x e c u t i b l e $ (TARGET)
@echo
100 rm − f $ (TARGET)
$ (CC ) $ ( COMPILE FLAGS LINK) − o $ (TARGET ) $ ( OBJECTS ) \
$ ( LIBRARY FLAGS SOURCES ) $ ( SIMLIBS ) $ ( XLIBS ) $ ( LIBS )
#−−−−−−−−−−−−−−−−−−−−−−−−−−− #
105 # ’ make ’ t e m p l a t e f o r OBJECTS #
#−−−−−−−−−−−−−−−−−−−−−−−−−−− #
$ ( OBJECTS ) : $ (@: . o = . c ) s i m u l a t i o n . h
@echo
@echo C o m p i l i n g $@
110 @echo
$ (CC ) $ ( COMPILE FLAGS SOURCES ) $ ( LIBS ) $ (@: . o = . c )
all :
@make p r o g s − f $ (MYMAKE)
#−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−
115 # dependencies
#−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−−
alpha beta . o : alpha beta . c simulation . h
set toxin signature . o : set toxin signature . c simulation . h
set HH vector . o : set HH vector . c simulation . h
120 current . o : current . c simulation . h
sim . o : sim . c s i m u l a t i o n . h
graph color . o : graph color . c simulation . h
axis color . o : axis color . c simulation . h
check points . o : check points . c simulation . h
125 rkf5 plot . o : rkf5 plot . c simulation . h
function . o : function . c simulation . h
external force . o : external force . c simulation . h
run plot . o : run plot . c simulation . h
handle button release . o : handle button release . c simulation . h
130 set axiscolor . o : set axiscolor . c simulation . h
set graphcolor . o : set graphcolor . c simulation . h
set popupplot . o : set popupplot . c simulation . h
imagepopupcolor . o : imagepopupcolor . c simulation . h
imagepopupplot . o : imagepopupplot . c simulation . h
135 set active . o : set active . c simulation . h
set plot . o : set plot . c simulation . h
expose . o : expose . c s i m u l a t i o n . h
input . o : input . c simulation . h
resize . o : resize . c simulation . h
140 quit application . o : quit application . c simulation . h
349
image . o : image . c s i m u l a t i o n . h
scale . o : scale . c simulation . h
rotate . o : rotate . c simulation . h
popupdrawExposeCB . o : popupdrawExposeCB . c s i m u l a t i o n . h
145 popupdrawResizeCB . o : popupdrawResizeCB . c s i m u l a t i o n . h
p o pu p q u i t C B . o : p o p u p q u i t C B . c s i m u l a t i o n . h
setxcolor . o : setxcolor . c simulation . h
find named color . o : find named color . c simulation . h
force update . o : force update . c simulation . h
150 update color . o : update color . c simulation . h
rest . o : rest . c simulation . h
gates . o : gates . c simulation . h
toxin . o : toxin . c toxin . h
Hence after editing these two files as you wish, you recompile as follows: note in the listing below,
we have added carriage returns to avoid lines being too long.
[petersj@dagmar ClassicHH] make -f MakeApp

make[1]: Entering directory ‘/home/petersj/ProgramApps/CellModels/ClassicHH’
Compiling rkf5_plot.o
g++ -c -g -I/usr/X11R6/include -I/usr/X11R6/include -I/home/petersj/programs/Ji

mIncludes -I -I/home/petersj/ProgramsApp/sim_ode -lm rkf5_plot.c
rkf5_plot.c: In function ‘void oderkf5_plot (DOUBLE_VECTOR &,
DOUBLE_VECTOR &, DOUBLE_VECTOR &, double, double, double, double,
application_data *, _WidgetRec *)’:
rkf5_plot.c:49: warning: initialization to ‘int’ from ‘double’
rkf5_plot.c:49: warning: argument to ‘int’ from ‘double’
g++: -lm: linker input file unused since linking not done
Compiling run_plot.o
g++ -c -g -I/usr/X11R6/include -I/usr/X11R6/include

-I/home/petersj/programs/Ji
mIncludes -I -I/home/petersj/ProgramsApp/sim_ode -lm run_plot.c
g++: -lm: linker input file unused since linking not done
Creating the Executible ode
rm -f ode
g++ -g -I/usr/X11R6/include -I/usr/X11R6/include
-I/home/petersj/programs/JimIncludes -I
-I/home/petersj/ProgramsApp/sim_ode
-o ode current.o sim.o popupdrawExposeCB.o
popupdrawResizeCB.o setxcolor.o find_named_color.o
update_color.o force_update.o popupquitCB.o graph_color.o
axis_color.o check_points.o rkf5_plot.o function.o
external_force.o run_plot.o set_plot.o
350
handle_button_release.o imagepopupplot.o
set_popupplot.o imagepopupcolor.o set_axiscolor.o
set_graphcolor.o set_active.o expose.o input.o
resize.o quit_application.o image.o rest.o gates.o \
-L/home/petersj/programs/JimLibs -L/usr/X11R6/lib
-L/usr/X11R6/lib -lrkf5parobjects -ldoublevec2 -ldoublevec1
-lintvec2 -lintvec1 -lbox -lshape -lXm -lXp -lXpm
-lXaw -lXt -lXmu -lXext -lX11 -lm
make[1]: Leaving directory ‘/home/petersj/ProgramApps/CellModels/ClassicHH’
[petersj@dagmar ClassicHH]
Then to run the simulation, you type ode at the prompt. You will then see the popup windows for
the graph that is generated and see some terminal output in the window you start the simulation
in. The output shown here discards some of the X Window diagnostic code that is still present in
the simulation for our debugging purposes. First, we see the battery voltages followed by all the
sodium and potassium conductances we will be using. For example, if we use a maximum sodium
conductance of 60 and a maximum potassium conductance of 18, we would see the following output
to the screen:
[petersj@dagmar SimpleHH] ode
Let’s plot the ODE data:

Let’s plot action potential:
Fahrenheit Temperature is 43.34
In rest calculation: parameters are p = 120 36 0.02 55.54 -72.7004 -49
g_leak_bar = 0.0306363
Initial activation and inactivations are
m_NA(0) = 0.0258481
h_NA(0) = 0.777813
m_K1(0) = 0.232349
E_NA = 55.54
E_K = -72.7004
E_M = -65.9
E_L = -49
g_leak_bar = 0.0306363
//we use the

//sodium conductance of 60 and the
//potassium conductance of 18.
//we start with the nominal leakage conductance
//of 0.0306, then recalculate the leakage conductance
//with a call to the rest function.
//the other numbers are the battery voltages
In rest calculation: parameters are
351
p = 60 18 0.0306363 55.54 -72.7004 -49
//we then recalculate the leakage conductance

// to be
g_leak_bar = 0.0153182
//we find the initial values for the state vector

m_NA(0) = 0.0258481
h_NA(0) = 0.777813
m_K1(0) = 0.232349
//this gives us the initial state

yinit = -65.9 0.0258481 0.777813 0.232349
//and we have reset p to use the new leakage conductance

parameters = 60 18 0.0153182 55.54 -72.7004 -49
//we now print out some of the simulation results

tinit = 0
tfinal = 25
NUMBER_PLOT_POINTS = 1000
HPLOT = 0.025
(t,y[0]) = 0.025,-65.7694
(t,y[0]) = 0.05,-65.6288
(t,y[0]) = 0.075,-65.4782
(t,y[0]) = 0.1,-65.3174
(t,y[0]) = 0.125,-65.1468
(t,y[0]) = 5.025,-58.583
(t,y[0]) = 10.025,-64.791
(t,y[0]) = 15.025,-66.7159
(t,y[0]) = 20.025,-66.8509
Closed Output file
Finished with PLOT loop
17.6.6 The Development of An Action Potential:
Let’s examine how an action potential is generated with this model. We start with the excitation given
by external current as shown in Figure 17.5. As this current flows into the membrane, the membrane
begins to depolarize. The current flow of sodium and potassium through the membrane is voltage
dependent and so this increase in the voltage across the membrane causes changes in the ion gates. In
Figure 17.6, we see the voltage time trace in the left window and the superimposed plots of sodium
and potassium current on the right.
352
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 17.6: Simulataneous Sodium and Potassium Currents During A Pulse
Recall the ion current equations: The nonlinear conductance is modeled by
M ax 3
M ax
gK (V, t) = gK HK 4 (V, t)
and the full currrent equations are
IN a = gN A (V, t)(V (t) − EN A )
IK = gK (V, t)(V (t) − EK )
IL = gL (V, t)(V (t) − EL )
The conductance is in micro Siemens or units of 10−6 1/ohms. Time is in milliseconds or 10−3 seconds
and voltage is in millivolts or 10−3 volts. The currents here are thus in units of 10−9 amps or naonamps.
For our stated inner and outer sodium and potassium concentrations, our simulation uses the ion
353
battery voltages EN A = 55.54 mV and EK = −72.7004 mV. Let’s use g0N a = 126.667 and 38.0
for g0K = 34.0. The computed leakage conductance is then gL = 0.0323383 for our chosen leakage
voltage of EL = −49.0. The specific ion currents are then
IN a = 126.667 MN A 3 (V, t) HN A (V, t) (V (t) − 55.54)
IK = 38.0 HK 4 (V, t) (V (t) + 72.7004)
IL = 0.0323383(V (t) + 49.0)
The largest the MN A 3 HN A and HK 4 terms can be is 1, the minimum voltage is essentially the equilib-
rium voltage −65.9 mV and the maximum voltage is roughly 70 mV. Hence, the ion currents should
lie in the ranges
IN a ∈ 126.667 [−121.44, 14.46]
IK ∈ 38.0 [6.104, 142.704]
IL ∈ 0.027647[−16.9, 119.0]
Now to get a better estimate on how large these currents can be, we can look at the time traces of
MN A , HN A and MK . These are shown in Figure 17.7. In the far left panel, you see the MN A curve
and on the right, the HN A curve. In a separate illustration, Figure 17.8, we see the time trace of
the product MN A 3 HN A that is used in the sodium conductance model. We then show the potassium
activation MK and the product M4K used in the potassium conductance model in Figure 17.8. We
can clearly see that the products MN A 3 HN A and M4K have maximum values of about 0.4. Hence,
the effective range is
354
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IN a = gN A (V, t)(V (t) − EN A )
 
 
 

 IK = gK (V, t)(V (t) − EK ) 

IL = gL (V, t)(V (t) − EL )
Figure 17.7: Sodium Activation and Inactivation Variables During a Pulse.
IN a ∈ 126.667 [−48.576, 5.784] = [−6152.976, 732.64]
IK ∈ 38.0 [2.44, 57.08] = [97.92, 2169.04]
IL ∈ 0.027647[−6.76, 47.6] = [−0.187, 1.316]
Of course, the actual traces have values that are much less; in this example, both the sodium and
potassium current peak at about 1000 na in absolute value. Note the sodium current is negative and
the potassium current is positive. To see how the sodium current activates first and then the potassium
current, we can plot the absolute value of IN a and IK simultaneously. This is done in Figure 17.10.
355
Figure 17.8: The value of m3N a hN a is shown for the pulse.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 17.9: The activation for potassium is labeled mK and it occurs in the potassium conductance
model as (mK )4 . The right panel shows mK and the left panel shows the time trace of (mK )4 .
356
Figure 17.10: The absolute value of the sodium current and the regular potassium current are plotted
together so that the lag in potassium currrent initiation is easier to see
357
17.7 Hodgkin - Huxley Matlab Simulation Code:
Our code in MatLab is more simplistic than the code used in the C++ implementation as we use the
Runga - Kutte Order 4 integrator rather than the step size adjusting Fehlberg code. Thus, we simply
integrate the equations using a fixed time step repeatedly with a Runga-Kutte method of order 4.
17.7.1 SolveSimpleHH.m
The code to manage the solution of the ODE is given below:
Listing 17.22: Managing The MatLab Hodgkin - Huxley Simulation

f u n c t i o n [ t v a l s , g NA , g K , V, m NA , h NA , n K ] = . . .
SolveSimpleHH ( fname , iename , t 0 , y0 , h , k , n , g Kmax , g NAmax )
%
5 % We u s e a s i m p l e Runge−K u t t a scheme
% u s i n g t h e Matlab f u n c t i o n below :
%
%f u n c t i o n [ t v a l s , g Na , g K , V ] = HHFixedRK ( fname , iename , t 0 , y0 , h , k , n )
%
10 % Gives approximate s o l u t i o n to
% y ’( t ) = f ( t , y( t ))
% y ( t 0 ) = y0
% u s i n g a k t h o r d e r RK method
%
15 % t0 i n i t i a l time
% y0 initial state
% h stepsize
% k RK o r d e r 1<= k <= 4
% n Number o f s t e p s t o t a k e
20 %
% tvals t i m e v a l u e s o f form
% t v a l s ( j ) = t 0 + ( j −1)∗h , 1 < = j <= n
%
% g Na = s o d i u m c o n d u c t a n c e
25 % g K = potassium conductance
% V = membrane v o l t a g e
%
m NA = z e r o s ( 1 , n ) ;
h NA = z e r o s ( 1 , n ) ;
30 n K = zeros (1 , n ) ;
g Na = z e r o s ( 1 , n ) ;
g K = zeros (1 , n ) ;
V = zeros (1 , n ) ;
358
35 [ t v a l s , y v a l s ] = HHFixedRK ( fname , iename , t 0 , y0 , h , k , n ) ;
%
% store values in physical variables
%
40 V = yvals (1 ,1: n );
m NA = yvals (2 ,1: n );
h NA = yvals (3 ,1: n );
n K = yvals (4 ,1: n );
45 %
% Compute g Na and G K
%
for i = 1 : n
u = m NA( i ) ∗m NA( i ) ∗m NA( i ) ∗ h NA ( i ) ;
50 g NA ( i ) = g NAmax∗u ;
end
for i = 1 : n
u = n K ( i )∗ n K ( i )∗ n K ( i )∗ n K ( i ) ;
55 g K ( i ) = g Kmax ∗ u ;
end
17.7.2 The Hodgkin - Huxley Dynamics:
The Hodgkin-Huxley dynamics are encoded in the function below:

hh2simplehh
Listing 17.23: The MatLab Hodgkin - Huxley Dymanics: simpleHH.m

f u n c t i o n f = simpleHH ( t , y , IE )
% S t a n d a r d Hodgkin − H u x l e y Model
% voltage mV
5 % current na
% time ms
% c o n c e n t r a t i o n mM
% conductance micro Siemens
% capacitance nF
10 % ===============================================
% y vector assignments
% ===============================================
% y (1) = V
% y ( 2 ) = m NA
15 % y ( 3 ) = h NA
% y (4) = m K
%
% set size of f
359
%
20
f = zeros ( 1 , 4 ) ;
% ===============================================
% f vector assignments
25 % ===============================================
% y ( 1 ) = V dynamics
% y ( 2 ) = m NA d y n a m i c s
% y ( 3 ) = h NA d y n a m i c s
% y ( 4 ) = m K dynamics
30 %
% ================================================
% F a s t Sodium C u r r e n t
% ===============================================
% ================================================
35 % Constants for Equilibrium Voltage Calculations
% ===============================================
%
% Rydberg ’ s C o n s t a n t
40 R = 8.31;
% Kelvin Temperature ; use 9 . 3 degrees C e l s i u s
T = 22.2;
% Faraday ’ s c o n s t a n t
F = 9 . 6 4 9 e +4;
45 %
% Compute N e r n s t v o l t a g e s o f E K and E Na
% v o l t a g e = N e r n s t ( v a l e n c e , T e m p e r a t u r e , InConc , OutConc )
%
50 %
% Sodium
%
NA O = 4 9 1 . 0 ;
NA I = 5 0 . 0 ;
55 E NA = N e r n s t ( 1 , T , NA I , NA O ) ;
%
% Potassium
%
60 K O = 20.11;
K I = 400.0;
E K = Nernst (1 ,T, K I , K O ) ;
65 % max c o n d u c t a n c e f o r NA
g NA bar = 1 2 0 . 0 ;
% max c o n d u c t a n c e f o r K
360
g K bar = 3 . 6 0 ;
70
%
% a c t i v a t i o n / i n a c t i v a t i o n p a r a m e t e r s f o r NA
%
% alpha mNA , beta mNA
75 %
sum = y ( 1 ) + 3 5 . 0 ;
i f sum > 0
alpha mNA = −0.10∗ sum / ( exp(−sum / 1 0 . 0 ) − 1 . 0 ) ;
else
80 alpha mNA = −0.10∗ exp ( sum / 1 0 . 0 ) ∗ sum / ( 1 . 0 − exp ( sum / 1 0 . 0 ) ) ;
end
%
sum = y ( 1 ) + 6 0 . 0 ;
i f sum > 0
85 beta mNA = 4 . 0 ∗ exp ( −sum / 1 8 . 0 ) ;
else
beta mNA = 4 . 0 ∗ exp ( −sum / 1 8 . 0 ) ;
end
%
90 m N A i n f i n i t y = alpha mNA / ( alpha mNA+beta mNA ) ;
t m NA = 1 . 0 / ( alpha mNA+beta mNA ) ;
%
f (2) = ( m N A i n f i n i t y − y ( 2 ) ) / t m NA ;
95 %
% a c t i v a t i o n , i n a c t i v a t i o n p a r a m e t e r f o r I NA
%
% alpha hNA , beta mNA
%
100 sum = ( y ( 1 ) + 6 0 . 0 ) / 2 0 . 0 ;
i f sum < 0
alpha hNA = 0 . 0 7 ∗ exp ( −sum ) ;
else
alpha hNA = 0 . 0 7 ∗ exp ( −sum ) ;
105 end
%
sum = y ( 1 ) + 3 0 . 0 ;
i f sum>0
beta hNA = 1 . 0 / ( 1 . 0 + exp(−sum / 1 0 . 0 ) ) ;
110 else
end
%
115 t h NA = 1 . 0 / ( alpha hNA + beta hNA ) ;
f (3) = ( h N A i n f i n i t y − y ( 3 ) ) / t h NA ;
361
% I NA c u r r e n t
120 %
I NA = g NA bar ∗ ( y (1) −E NA ) ∗ y ( 2 ) ∗ y ( 2 ) ∗ y ( 2 ) ∗ y ( 3 ) ;
%
% a c t i v a t i o n / i n a c t i v a t i o n parameters for K
125 %
% alpha mK
%
sum = y ( 1 ) + 5 0 . 0 ;
i f sum > 0
130 alpha mK = −0.01∗ sum / ( exp(−sum / 1 0 . 0 ) − 1 . 0 ) ;
else
alpha mK = −0.01∗ exp ( sum / 1 0 . 0 ) ∗ sum / ( 1 . 0 − exp ( sum / 1 0 . 0 ) ) ;
end
sum = ( y ( 1 ) + 6 0 . 0 ) ∗ 0 . 0 1 2 5 ;
135 i f sum > 0
beta mK = 0 . 1 2 5 ∗ exp ( −sum ) ;
else
beta mK = 0 . 1 2 5 ∗ exp ( −sum ) ;
end
140 t m K = 1 . 0 / ( alpha mK + beta mK ) ;
m K infinity = alpha mK / ( alpha mK + beta mK ) ;
f (4) = ( m K infinity − y ( 4 ) ) / t m K ;
%
145 % I K current
%
I K = g K b a r ∗ ( y (1) − E K ) ∗ y ( 4 ) ∗ y ( 4 ) ∗ y ( 4 ) ∗ y ( 4 ) ;
%
150 % l e a k a g e c u r r e n t : run r e s t .m t o f i n d a p p r o p r i a t e g L v a l u e
%
g leak = −0.0013;
E leak = −50.0;
155 %
% I L current
%
I l e a k = g l e a k ∗ ( y (1) − E l e a k ) ;
160 %
% Cell Capacitance
%
C M = 1.0;
s = f e v a l ( IE , t ) ;
165 % s = 0;
f ( 1 ) = ( s − I NA − I K − I l e a k ) / C M ;
362
Initial Condtions:
The code to compute the initial conditions is as follows:
Listing 17.24: Initializing The Simulation: rest.m

f u n c t i o n [ g L , m N A i n f i n i t y , h N A i n f i n i t y , m K i n f i n i t y ] = r e s t ( E L , V R , g NA bar , g
%
% inputs :
% E L = leakage voltage
5 % g N A b a r = maximum s o d i u m c o n d u c t a n c e
% g K b a r = maximum p o t a s s i u m c o n d u c t a n c e
% V R = rest voltage
%
% outputs :
10 % g L = leakage conductance
%
% ==================================================
% Constants f o r Ion Equilibrium Voltage C a l c u l a t i o n s
% ==================================================
15 %
% Rydberg ’ s C o n s t a n t
R = 8.31;
% Kelvin Temperature ; use 9 . 3 degrees C e l s i u s
T = 22.2;
20 % Faraday ’ s c o n s t a n t
F = 9 . 6 4 9 e +4;
%
% Compute N e r n s t v o l t a g e s o f E K and E Na
% v o l t a g e = N e r n s t ( v a l e n c e , T e m p e r a t u r e , InConc , OutConc )
25 %
%
% Sodium
%
30 NA O = 4 9 1 . 0 ;
NA I = 5 0 . 0 ;
E NA = N e r n s t ( 1 , T , NA I , NA O )
%
35 % Potassium
%
K O = 20.11;
K I = 400.0;
E K = Nernst (1 ,T, K I , K O)
40
%
% a c t i v a t i o n / i n a c t i v a t i o n p a r a m e t e r s f o r NA
%
% alpha mNA , beta mNA
363
45 %
sum = V R + 3 5 . 0 ;
i f sum > 0
alpha mNA = −0.10∗ sum / ( exp(−sum / 1 0 . 0 ) − 1 . 0 ) ;
50 else
alpha mNA = −0.10∗ exp ( sum / 1 0 . 0 ) ∗ sum / ( 1 . 0 − exp ( sum / 1 0 . 0 ) ) ;
end
%
sum = V R + 6 0 . 0 ;
55 i f sum > 0
beta mNA = 4 . 0 ∗ exp ( −sum / 1 8 . 0 ) ;
else
beta mNA = 4 . 0 ∗ exp ( −sum / 1 8 . 0 ) ;
end
60 %
m N A i n f i n i t y = alpha mNA / ( alpha mNA+beta mNA )
%
% a c t i v a t i o n , i n a c t i v a t i o n p a r a m e t e r f o r I NA
65 %
% alpha hNA , beta mNA

%
sum = ( V R + 6 0 . 0 ) / 2 0 . 0 ;
70 i f sum < 0
alpha hNA = 0 . 0 7 ∗ exp ( −sum ) ;
else
alpha hNA = 0 . 0 7 ∗ exp ( −sum ) ;
end
75 %
sum = V R + 3 0 . 0 ;
i f sum>0
beta hNA = 1 . 0 / ( 1 . 0 + exp(−sum / 1 0 . 0 ) ) ;
else
80 beta hNA = exp ( sum / 1 0 . 0 ) / ( exp ( sum / 1 0 . 0 ) + 1 . 0 ) ;
end
%
h N A i n f i n i t y = alpha hNA / ( alpha hNA + beta hNA )
85 %
% I NA c u r r e n t
%
I NA = g NA bar ∗ ( V R−E NA ) ∗ m N A i n f i n i t y ∗ m N A i n f i n i t y ∗ m N A i n f i n i t y ∗ h N A i n f i n i t y
90 %
% a c t i v a t i o n / i n a c t i v a t i o n parameters for K
%
% alpha mK
%
364
95 sum = V R + 5 0 . 0 ;
i f sum > 0
alpha mK = −0.01∗ sum / ( exp(−sum / 1 0 . 0 ) − 1 . 0 ) ;
else
alpha mK = −0.01∗ exp ( sum / 1 0 . 0 ) ∗ sum / ( 1 . 0 − exp ( sum / 1 0 . 0 ) ) ;
100 end
sum = ( V R + 6 0 . 0 ) ∗ 0 . 0 1 2 5 ;
i f sum > 0
beta mK = 0 . 1 2 5 ∗ exp ( −sum ) ;
else
105 beta mK = 0 . 1 2 5 ∗ exp ( −sum ) ;
end
m K infinity = alpha mK / ( alpha mK + beta mK )
110 %
% I K current
%
I K = g K b a r ∗ ( V R−E K ) ∗ m K i n f i n i t y ∗ m K i n f i n i t y ∗ m K i n f i n i t y ∗ m K i n f i n i t y
115 numerator = −I NA − I K ;
denominator = V R − E L ;
%
% compute g L
120 %
% N o t e we want
% I NA + I K + g L ∗ ( V R − E L ) = 0
% w h i c h g i v e s t h e e q u a t i o n b e l o w a s s u m i n g we a r e g i v e n E L .
125 %
g L = − ( I NA + I K ) / ( V R − E L ) ;
Managing The ODE Integration:
The code that manages the call to a fixed Runga-Kutte order method from an earlier chapter has been
modified to accept an argument which is the name of the function which models the current injection.
Listing 17.25: The MatLab Fixed Runga - Kutte Method

f u n c t i o n [ t v a l s , y v a l s ] = HHFixedRK ( fname , iename , t 0 , y0 , h , k , n )
%
% Gives approximate s o l u t i o n to
% y ’( t ) = f ( t , y( t ))
5 % y ( t 0 ) = y0
% u s i n g a k t h o r d e r RK method
365
%
% t0 i n i t i a l time
% y0 initial state
10 % h stepsize
% k RK o r d e r 1<= k <= 4
% n Number o f s t e p s t o t a k e
%
% tvals t i m e v a l u e s o f form
15 % t v a l s ( j ) = t 0 + ( j −1)∗h , 1 < = j <= n
% yvals approximate s o l u t i o n
% yvals ( : j ) = approximate s o l u t i o n at
% t v a l s ( j ) , 1 <= j <= n
% fname name o f d y n a m i c s f u n c t i o n
20 % i e n a m e name o f c u r r e n t i n j e c t i o n f u n c t i o n
%
tc = t0 ;
yc = y0 ;
tvals = tc ;
25 yvals = zeros (4 , n ) ;
y v a l s ( 1 : 4 , 1 ) = t r a n s p o s e ( yc ) ;
f c = f e v a l ( fname , t c , yc , i e n a m e ) ;
f o r j = 1 : n−1
[ t c , yc , f c ] = HHRKstep ( fname , iename , t c , yc , f c , h , k ) ;
30 y v a l s ( 1 : 4 , j + 1 ) = t r a n s p o s e ( yc ) ;
tvals = [ tvals tc ];
end
17.7.3 Modifications to The Built In Runga - Kutte Function:
The actual Runga-Kutte code was also modified to allow the name of the current injection function to
be entered as an argument.
Listing 17.26: Adding Injection Current To The Runga - Kutte Code

f u n c t i o n [ tnew , ynew , fnew ] = HHRKstep ( fname , iename , t c , yc , f c , h , k )
%
% fname t h e name o f t h e r i g h t hand s i d e f u n c t i o n f ( t , y )
% t i s a s c a l a r u s u a l l y c a l l e d t i m e and
5 % y is a vector of size d
% yc approximate s o l u t i o n to y ’ ( t ) = f ( t , y ( t ) ) at t=t c
% fc f ( tc , yc )
% h The t i m e s t e p
% k The o r d e r o f t h e Runge−K u t t a Method 1 <= k <= 4
10 %
% tnew t c +h
% ynew approximate s o l u t i o n a t tnew
% fnew f ( tnew , ynew )
366
%
15 i f k==1
k1 = h ∗ f c ;
ynew = yc +k1 ;
e l s e i f k==2
k1 = h ∗ f c ;
20 k2 = h ∗ f e v a l ( fname , t c + ( h / 2 ) , yc + ( k1 / 2 ) , i e n a m e ) ;
ynew = yc + ( k1+k2 ) / 2 ;
e l s e i f k==3
k1 = h ∗ f c ;
k2 = h ∗ f e v a l ( fname , t c + ( h / 2 ) , yc + ( k1 / 2 ) , i e n a m e ) ;
25 k3 = h ∗ f e v a l ( fname , t c +h , yc−k1 +2∗ k2 , i e n a m e ) ;
ynew = yc + ( k1 +4∗ k2+k3 ) / 6 ;
e l s e i f k==4
k1 = h ∗ f c ;
k2 = h ∗ f e v a l ( fname , t c + ( h / 2 ) , yc + ( k1 / 2 ) , i e n a m e ) ;
30 k3 = h ∗ f e v a l ( fname , t c + ( h / 2 ) , yc + ( k2 / 2 ) , i e n a m e ) ;
k4 = h ∗ f e v a l ( fname , t c +h , yc +k3 , i e n a m e ) ;
ynew = yc + ( k1 +2∗ k2 +2∗ k3+k4 ) / 6 ;
else
d i s p ( s p r i n t f ( ’The RK method %2d order is not allowed!’ , k ) ) ;
35 end
tnew = t c +h ;
fnew = f e v a l ( fname , tnew , ynew , i e n a m e ) ;
17.7.4 RunTime Results:
For this simulation, we will use a Celsius temperature of 22. We also use a maximum sodium con-
ductance of 120.0 and a maximum potassium conductance of 3.6. There are a few things we have to
watch for when we run a simulation:
• The Celsius temperature is actually typed into the code files simpleHH.m and rest.m. So
changing this temperature means you have to edit and change a line in both files.
• The maximum sodium and potassium conductances are also hard coded into the files sim-
pleHH.m and rest.m. So changing these values requires editing these two files also.
• Once values of temperature and maximum conductances are chosen, run rest.m to determine the
value of gL that ensures no current flows across the cell membrane when there is no external cur-
rent. This funtion call also returns the initial values for the Hodgkin - Huxley dynamical system.
367
The line [g L,m NA infinity,h NA infinity,m K infinity] = rest(E L,V R,g NA bar,g K bar) ×
plus the initialization V R = -70 gives the initial condition for the Hodgkin -Huxley dynamical
system to be
   
 y[1]   E R 
   
   
 y[2]   m NA infinity 
   
  =  .
   
 y[3]   h NA infinit 
   
   
   
y[4] m K infinity
The value of gL returned must be typed into the appropriate place in the file simpleHH.m.
• Once the above steps have been done, we are ready to run the simulation.
We ran our simple simulation using this session:
Listing 17.27: A Sample Simple Hodgkin - Huxley Simulation

<M A T L A B >
C o p y r i g h t 1 9 8 4 − 2 0 0 4 The MathWorks , I n c .
V e r s i o n 7 . 0 . 0 . 1 9 9 0 1 ( R14 )
May 0 6 , 2 0 0 4
5
To g e t s t a r t e d , s e l e c t MATLAB Help o r Demos from t h e Help menu .
>> path ( path , ’/users/petersj/public_html/m450/HH’ ) ;

10 >> E L = − 5 0 ;
>> V R = − 7 0 ;
>> g NA bar = 1 2 0 . 0 ;
>> g K b a r = 3 . 6 ;
>> [ g L , m N A i n f i n i t y , h N A i n f i n i t y , m K i n f i n i t y ] = r e s t ( E L , V R , g NA bar , g K b a r )
15
E NA = 58.0840
E K = −76.0304
m NA infinity = 0.0154
h NA infinity = 0.8652
20 I NA = −0.0485
m K infinity = 0.1810
I K = 0.0233
g L = −0.0013
m NA infinity = 0.0154
368
25 h NA infinity = 0.8652
m K infinity = 0.1810
>> [ t v a l s , g NA , g K , V, m NA , h NA , m K ] = . . .
SolveSimpleHH ( ’simpleHH’ , ’IE’ , 0 . 0 , [ − 7 0 . 0 , m N A i n f i n i t y , h N A i n f i n i t y , m K i n f i n i t y
30 0.01 ,4 ,10000 ,120.0 ,3.6);
>> plot ( t v a l s , V, ’r-’ ) ;

>> print − dpng a c t i o n p o t e n t i a l . png ;
>> plot ( t v a l s , m NA , ’r-’ ) ;
35 >> print − dpng m NA102005 . png
>> plot ( t v a l s , h NA , ’r-’ ) ;
>> print − dpng h NA102005 . png ;
>> plot ( t v a l s , m K , ’r-’ ) ;
>> print − dpng m K102005 . png ;
40
>> I NA = 1 2 0 . 0 . ∗ m NA . ∗ m NA . ∗ m NA . ∗ h NA . ∗ ( V − 5 8 . 0 8 4 0 ) ;
>> I K = 3 . 6 . ∗ m K . ∗ m K . ∗ m K . ∗ m K . ∗ ( V+ 7 6 . 0 3 0 4 ) ;
>> p l o t ( t v a l s , I NA , ’b-’ , t v a l s , I K , ’r-’ ) ;
>> p r i n t − dpng HHI NA−I K . png
For all of these results, we use the applied current given by the code IE.m.
Listing 17.28: The Injected Current Pulse

f u n c t i o n s = IE ( t )
%
%
%
5 n = length ( t ) ;
s = zeros (1 , n ) ;
for i =1: n
s( i ) = 0;
i f t ( i ) >= 10 & t ( i ) <= 10.62
10 s ( i ) = 100;
end
end
This pulse applies a constant current of 100 namps between on the time interval [10.0, 10.62]. Other-
wise, it is zero.
We perform the necessary Nernst voltage calculations with the function given in Nernst.m.
Listing 17.29: Computing the Nernst Voltage

%
%
369
Figure 17.11: Membrane Voltage vs Time:
5 R = 8.31;
F = 96480.0;
%
%
In Figure ( 17.11), we see the membrane voltage versus time curve that results from the application
of this injected current.
Note we see a nice action potential here. In Figure 17.12(a) and Figure 17.12(b), we show the activa-
tion and inactivation variables for sodium.
In Figure 17.13(a), we show the activation variable for potassium. It is also instructive to look at
the ion currents and conductances during the pulses. In Figure ( 17.13(b)), we see the sodium and
potassium currents plotted simultaneously.
Note that the sodium current is positive while the potassium current is negative. If you look closely,
you can see the potassium current lags behind the sodium one. Now let’s plot the τmN A and m∞
NA
values for mN A in our simulation. We start the session using the same commands as we did in
Listing 17.27. We then add the commands to do the new desired plots.
370
(a) Activation vs. Time (b) Inactivation vs Time
Figure 17.12: Sodium Dynamics
(a) Potassium Activation vs. Time (b) Sodium and Potassium Currents vs Time:
Figure 17.13: Sodium and Potassium Behavior
371
Figure 17.14: m Time Constant and Asymptotic Value vs Time:
Listing 17.30: A Second Sample Simple Hodgkin - Huxley Simulation

>> taumNA = 1 . 0 . / ( alphamNA (V) + betamNA (V ) ) ;
>> p l o t ( t v a l s , taumNA , ’g-’ ) ;
>> p r i n t − dpng taumNA−t i m e . png ;
5 >> mNAasymptote = alphamNA (V ) . / ( alphamNA (V) + betamNA (V ) ) ;

>> p l o t ( t v a l s , mNAasymptote , ’r-’ ) ;
>> p r i n t − dpng mNAasymptote−t i m e . png
>> p l o t ( t v a l s , taumNA , ’g-’ , t v a l s , mNAasymptote , ’r-’ ) ;

10 >> p r i n t − dpng taumNA−mNAasymptote . png ;
NA
The values of τm and m∞
N A versus time are plotted simulateneously in Figure 17.14.
17.7.5 Exercise:
Exercise 1 Run the Hodgkin - Huxley simulation as has been done in the work above and write a
complete report in your favorite editor which includes the following things:
Study One: maximum sodium conductance is 120 and maximum potassium conductance is 3.6 1.
The plots of voltage, m NA, h NA and m K versus time for 100 mSec.
2. The plots of the time constant and the asymptotic value for m NA, h NA and m K versus
time.
3. The plots of sodium and potassium current versus time.
372
Figure 17.15: Action Potentials (120 Maximum Sodium Conductance In Red) (20 Maximum Sodium
Conductance In Blue)
Study Two: maximum sodium conductance is 20.0 and maximum potassium conductance is 3.6
Note that for this study, you need to run rest.m to reset the value of gL to use in simpleHH.m.
You also need to to alter the value of the maximum sodium conductance in simpleHH.m.
1. The plots of voltage, m NA, h NA and m K versus time for 100 ms overlayed on the plots
from Study One.
2. The plots of the time constant and the asymptotic value for m NA, h NA and m K versus
time overlayed on the plots from Study One.
3. The plots of sodium and potassium current versus time overlayed on the plots from Study
One.
You should see overlaid action potential plots like shown in Figure 17.15. The red curve is the
action potential for the 120.0 value of maximum sodium conductance, while the blue curve is
the plot for the value of 20.0 for Study Two.
17.8 Setting Up A Large C++ Simulation Study:
We now set up a parametric study which computes 100 different data runs for different values of the
maximum sodium and potassium conductances. For each choice of maximum sodium and potassium
373
conductance, we compute a new value of the leakage conductance so that we are sure that there will
be no current across the membrane at equilibrium potential. The code listed in Listing 17.16 needs to
be modified to handle the looping that is required over the choices of sodium and potassium maximum
conductance we will use. We do this in the code presented below in Listing 17.31.
Listing 17.31: Setting Up A Parametric Study

int plot type ;
/ ∗========================================
S e t up p a r a m e t e r s f o r ode i n t e g r a t i o n
========================================∗ /
5 int simsize = 10;
DOUBLE VECTOR GNA( s i m s i z e ) ;
DOUBLE VECTOR GK( s i m s i z e ) ;
double g n a l o w = 0 . 5 ∗ g NA bar ;
10 double gk low = 0 . 5 ∗ g K1 bar ;
double g n a h i g h = 1 . 5 ∗ g NA bar ;
double gk high = 1 . 5 ∗ g K1 bar ;
double gna width = gna high − gna low ;
double gk width = gk high − gk low ;
15
/ / r a n g e i s [ gn a lo w , g n a h i g h ]
/ / range i s [ gk low , g k h i g h ]
f o r ( i n t u = 0 ; u<s i m s i z e ; + + u ) {
GNA[ u ] = g n a l o w + u ∗ g n a w i d t h / ( s i m s i z e − 1 ) ;
20 GK[ u ] = g k l o w + u ∗ g k w i d t h / ( s i m s i z e − 1 ) ;
c o u t << "GNA[" << u << "] = " << GNA[ u ] < < e n d l ;
c o u t << "GK[" << u << "] = " << GK[ u ] < < e n d l ;
}
25 d o u b l e ymin ;
d o u b l e ymax ;
f o r ( i n t u = 0 ; u<s i m s i z e ; + + u ) {
f o r ( i n t v = 0 ; v<s i m s i z e ; + + v ) {
30 p [ 0 ] = GNA[ u ] ;
p [ 1 ] = GK[ v ] ;
r e s t (E M, p , q ) ;
g leak bar = p [2];
plot type = 0;
35 f o r ( i n t uu = 0 ; uu <19;++ uu ) {
i f ( p l o t t y p e ==uu ) {
ymin = Low Range [ uu ] ;
ymax = High Range [ uu ] ;
}
40 }
hinit = 1 . 0 e −8;
374
tinit = 0.00;
tend = 25.0;
tol = 1 . 0 e −12;
45 T−>PLOT−>p l o t t y p e = p l o t t y p e ;
T−>PLOT−>x minimum = t i n i t ;
T−>PLOT−>x maximum = t e n d ;
T−>PLOT−>y minimum = ymin ;
T−>PLOT−>y maximum = ymax ;
50 y i n i t = INIT ;
y = INIT ;
c o u t << "yinit = " << y i n i t << e n d l ;
c o u t << "parameters = " << p << e n d l << e n d l ;
o d e r k f 5 p l o t ( y i n i t , y , p , t o l , t i n i t , tend , h i n i t , T ,w) ;
55 }
}
}
17.8.1 C++ Code: The Run-Time Code:
To run the simulation study, you type ode at the prompt. You will see the popup windows for the
graph that is generated and also some terminal output in the window you start the simulation in.
[petersj@dagmar SimpleHH] ode
Let’s plot the ODE data:

Let’s plot action potential:
Fahrenheit Temperature is 43.34
In rest calculation: parameters are p = 120 36 0.02 55.54 -72.7004 -49
g_leak_bar = 0.0306363
m_NA(0) = 0.0258481
h_NA(0) = 0.777813
m_K1(0) = 0.232349
E_NA = 55.54
E_K = -72.7004
E_M = -65.9
E_L = -49
g_leak_bar = 0.0306363
//these are all the sodium and potassium

//conductances we will be using
GNA[0] = 60 GK[0] = 18
GNA[1] = 73.3333 GK[1] = 22
GNA[2] = 86.6667 GK[2] = 26
GNA[3] = 100 GK[3] = 30
GNA[4] = 113.333 GK[4] = 34
375
GNA[5] = 126.667 GK[5] = 38

GNA[6] = 140 GK[6] = 42
GNA[7] = 153.333 GK[7] = 46
GNA[8] = 166.667 GK[8] = 50
GNA[9] = 180 GK[9] = 54
//This is then our first run: we use the

//first sodium conductance of 60 and the
//first potassium conductance of 18
//we start with the nominal leakage conductance
//of 0.0306
//the other numbers are the battery voltages
In rest calculation: parameters are
p = 60 18 0.0306363 55.54 -72.7004 -49
//we then recalculate the leakage conductance

g_leak_bar = 0.0153182
//we find the initial values for the state vector

m_NA(0) = 0.0258481
h_NA(0) = 0.777813
m_K1(0) = 0.232349
//this gives us the initial state

yinit = -65.9 0.0258481 0.777813 0.232349
//and we have reset p to use the new leakage conductance

parameters = 60 18 0.0153182 55.54 -72.7004 -49
//we now print out some of the simulation results

tinit = 0
tfinal = 25
NUMBER_PLOT_POINTS = 1000
HPLOT = 0.025
(t,y[0]) = 0.025,-65.7694
(t,y[0]) = 0.05,-65.6288
(t,y[0]) = 0.075,-65.4782
(t,y[0]) = 0.1,-65.3174
(t,y[0]) = 0.125,-65.1468
(t,y[0]) = 5.025,-58.583
(t,y[0]) = 10.025,-64.791
(t,y[0]) = 15.025,-66.7159
(t,y[0]) = 20.025,-66.8509
Closed Output file
Finished with PLOT loop
//we would then do this 99 more times!!
376
Figure 17.16: Parametric Study of Action Potentials: g N a ranges from 60 to 180 in 10 and g K ranges
from 18 to 54 in 10 uniform steps each. This gives a total of 100 different Action Potentials. All of
the currents were the response of the cell model to the synaptic pulse described in the text.
17.8.2 Analyzing the Parametric Study Results:
The parametric study above generates some interesting pictures. Recall that each of these simulation
runs use the synaptic current injected as in Figure 17.5. In Figure 17.16, we see all 100 generated
action potentials. Although the graph is indeed cluttered, we can see that certain sodium and potas-
sium conductance parameter settings do not generate a response as there is insufficient cell membrane
depolarization.
If we run the simulation with the parameters as set in run plot.c and rest.c, the full parametric
study generates the sodium currents of Figure 17.17.
The corresponding potassium currents shown in Figure 17.18 are very interesting. Note how high
they spike!
Finally, we show the leakage currents for our experiments in Figure 17.19 which are all relatively
modest in size; approximately 4 na at most.
377
Figure 17.17: Parametric Study of Sodium Currents: g N a ranges from 60 to 180 in 10 and g K ranges
from 18 to 54 in 10 uniform steps each. This gives a total of 100 different sodium currents. All of the
currents were the response of the cell model to the synaptic pulse described in the text.
Figure 17.18: Parametric Study of Potassium Currents: g N a ranges from 60 to 180 in 10 and g K
ranges from 18 to 54 in 10 uniform steps each. This gives a total of 100 different potassium currents.
All of the currents were the response of the cell model to the synaptic pulse described in the text.
378
Figure 17.19: Parametric Study of Leakage Currents: g N a ranges from 60 to 180 in 10 and g K ranges
from 18 to 54 in 10 uniform steps each. This gives a total of 100 different potassium currents. All of
the currents were the response of the cell model to the synaptic pulse described in the text.
17.8.3 Computing the Average Simulation Data:
If we compute the average variable time traces for this simulation, we can organize the results graph-
ically in a series of arrays. In Figure 17.20, we see the state vector averages.
In Figures 17.21 and Figure 17.22, we show the average time traces for the individual α and β pairs
which determine the nonlinear voltage and time models for all the activation and inactivation pairs.
The α and β models are then used to compute the asympotic values m∞ (here labeled as m∞
N A ), h∞
( here, h∞ ∞ ∞
N A ) and the associated time constants τm ( here, tN a ) and τh (here, tN a ). These graphs are
shown in Figure 17.23. Figure 17.24 shows similar average time traces for n∞ (here, m∞
K ) and taun
(here, t∞
N a ).
The average sodium and potassium currents are shown in Figure 17.25
The average sodium and potassium currents are shown in Figure 17.26
379
Figure 17.20: Average Time Traces For State Variables: The averages for the time traces for voltage,
the m and h activation parameters for the sodium gate model and the n activation parameter for the
potassium gate model for the 100 simulation runs are shown here
380
Figure 17.21: Average Variable Values For the α and β activation/ inactivation models for sodium.
These are the averages over all 100 simulation runs.
381
Figure 17.22: Average Variable Values For the α and β activation/ inactivation models for potassium.
These are the averages over all 100 simulation runs.
382
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Figure 17.23: The top row shows the average asymptotic values for m∞ and its time constant tm . The
second row shows the average asymptotic values for h∞ and its time constant th .
383
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Figure 17.24:
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Figure 17.25: Average Variable Values for the sodium and potassium currents.
384
Figure 17.26: Average Variable Values for the leakage current.
385
386
Part III
References
387
Bibliography
[1] J. Austyn and K. Wood. Principles of Cellular and Molecular Immunology. Oxford University
Press, 1993.
[2] J. Bower and D. Beeman. The Book of Genesis: Exploring Realistic Neural Models with the
GEneral NEural SImulation System. Springer TELOS, second edition edition, 1998.
[3] R. Eckert, D. Randall, and G. Augustine. Animal Physiology: Mechanisms and Adaptations. W.
H. freeman and Company, New York, third edition edition, 1998.
[4] M. Hadley. Endocrinology. Prentice Hall, 1996.
[5] Z. Hall. An Introduction to Molecular Neurobiology. Sinauer Associates Inc., Sunderland, MA,
1992.
[6] B. Hille. Ionic Channels of Excitable Membranes. Sinauer Associates Inc., 1992.
[7] B. Hille. Ionic Channels of Excitable Membranes, chapter Classical Biophysics of the Squid
Giant Axon, pages 23 – 58. Sinauer Associates Inc., 1992.
[8] D. Johnston and S. Miao-Sin Wu. Foundations of Cellular Neurophysiology. MIT Press, 1995.
[9] D. Johnston and S. Miao-Sin Wu. Foundations of Cellular Neurophysiology, chapter Hodgkin
and Huxley’s Analysis of the Squid Giant Axon, pages 143 – 182. MIT Press, 1995.
[10] W. Rall. Core Conductor Theory and Cable Properties of Neurons, chapter 3, pages 39 – 67.
Unknown, 1977.
[11] T. Stone. Neuropharmacology. W. H. Freeman, 1995.
389
[12] T. Weiss. Cellular Biophysics: Volume 1, Transport. MIT Press, 1996.
[13] T. Weiss. Cellular Biophysics: Volume 2, Electrical Properties. MIT Press, 1996.
[14] T. Weiss. Cellular Biophysics: Volume 2, Electrical Properties, chapter The Hodgkin - Huxley
Model, pages 163 – 292. MIT Press, 1996.
[15] W. Yamada, C. Koch, and P. Adams. Multiple Channels and Calcium Dynamics. In C. Koch
and I. Segev, editors, Methods of Neuronal Modeling, pages 97 – 134. MIT Press, 1987.
390

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A Primer On Excitable Nerve Cells

We are all made of the same stuff, Dewey.

Department of Mathematical Sciences

May 23, 2006

Notes On Neural Objects 1994 - 1995

Notes on Chained Neural Objects 1996

Notes on CMAC Neural Objects 1996

Class Notes: MTH SC 982 Spring 1997

Class Notes: MTH SC 450, MTH SC 827 Fall 2001

Research Notes: Air Force Rome IFSB, Summer 2005

1 Biological Information Processing 11

II Basic BioPhysics and Cellular Modeling 15

2 Some Chemistry Background: 17

2.1 Molecular Bonds: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

2.2 Bond Comparisons: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

2.3 Energy Considerations: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

3.1 Peptide Bonds: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

3.2 Chains of Amino Acids: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42

4.3 Complementary Base Pairing: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55

4.4 A Quick Look at How Proteins Are Made: . . . . . . . . . . . . . . . . . . . . . . . 58

5 Cell Membranes and Ion Movement: 63

5.1 Membranes in Cells: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63

5.2 The Physical Laws of Ion Movement: . . . . . . . . . . . . . . . . . . . . . . . . . 66

5.2.1 Ficke’s law of Diffusion: . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66

5.2.2 Ohm’s Law of Drift: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67

5.2.3 Einstein’s Relation: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68

5.2.4 Space Charge Neutrality: . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69

5.2.5 Ions, Volts and a Simple Cell: . . . . . . . . . . . . . . . . . . . . . . . . . 70

5.3 The Nernst - Planck Equation: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72

5.4 Equilibrium Conditions: The Nernst Equation: . . . . . . . . . . . . . . . . . . . . . 74

5.5 One Ion Nernst Computations in MatLab: . . . . . . . . . . . . . . . . . . . . . . . 78

6.1 The Cell Prior to KCl Disassociation: . . . . . . . . . . . . . . . . . . . . . . . . . 83

6.2 The Cell With K + Gates: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84

6.2.1 The Cell With Outer KCl Reduced: . . . . . . . . . . . . . . . . . . . . . . 85

6.3 The Cell With NaCl Inside and Outside Changes: . . . . . . . . . . . . . . . . . . . 86

6.4 The Cell with N a+ Gates: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87

6.5 The Nernst Equation For Two Ions: . . . . . . . . . . . . . . . . . . . . . . . . . . . 87

6.6 The Nernst Equation For More Than Two Ions: . . . . . . . . . . . . . . . . . . . . 90

6.7 Multiple Ion Nernst Computations in MatLab: . . . . . . . . . . . . . . . . . . . . . 92

7.1 Transport Mechanisms: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95

7.1.1 Ion Channels: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98

7.1.2 Passive Ion Transport: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98

7.1.3 Active Transport Using Pumps: . . . . . . . . . . . . . . . . . . . . . . . . 103

7.1.4 A Simple Compartment Model: . . . . . . . . . . . . . . . . . . . . . . . . 103

8 Movement of Ions Across Biological Membranes: 111

8.1 Membrane Permeability: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111

8.2 The Goldman-Hodgkin-Katz (GHK) Model: . . . . . . . . . . . . . . . . . . . . . . 116

8.3 The GHK Voltage Equation: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124

8.3.1 Examples: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126

8.4 The Effects of an Electrogenic Pump: . . . . . . . . . . . . . . . . . . . . . . . . . 128

8.5 Excitable Cells: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131

9 Lumped and Distributed Cell Models 141

9.1 Modeling Radial Current: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142

9.2 Modeling Resistance: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144

9.3 Longitudinal Properties: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145

9.4 Current in a Cable with a Thin Wall: . . . . . . . . . . . . . . . . . . . . . . . . . . 147

10 The Cable Model: 153

10.1 The Core Conductor Model Assumptions: . . . . . . . . . . . . . . . . . . . . . . . 154

10.2 Building the Core Conductor Model: . . . . . . . . . . . . . . . . . . . . . . . . . . 157

11 The Transient Cable Equations: 165

11.1 Deriving the Transient Cable Equation: . . . . . . . . . . . . . . . . . . . . . . . . 166

11.2 The Space and Time Constant of a Cable: . . . . . . . . . . . . . . . . . . . . . . . 169