ELEC4810: Introduction to

Biosensors and Bioinstrumentation

Lecture Notes – Set #2

ELEC4810

Textbook: Chapter 4
 Chapter 2
Biopotentials: Origins and Measurements

Main Topics:
Electrical Activity at Cellular Level
• bioelectric phenomena at the cellular level
• volume conductor potential distributions
• typical bioelectric sources: heart, brain, muscle, etc.

Recordings of bioelectric signals

• electrocardiogram (ECG)
• electromyogram (EMG)
• electroencephalogram (EEG)

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 Levels of Organization of Living Things

3
Cells as the living units of the body
• The basic living unit of the body is the cell, and each organ is an aggregate of
many different cells held together by intercellular supporting structures.
• Each type of cell is specially adapted to perform one particular function.
• The cell contains highly organized physical structure, many of which are called
organelles.
5
• The cell contains highly organized physical structure, many of
which are called organelles. Reconstruction of a typical cell
showing the internal organelles in the cytoplasm and in the
nucleus:

Cell
membrane
 Cells as the living units of the body
The entire body contains 37.2 trillion cells.

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 Cells as the living units of the body
• The basic living unit of the body is the cell, and each organ is an aggregate of
many different cells held together by intercellular supporting structures.
A current estimation of human total cell number calculated for a variety of organs
and cell types is about 3.72 × 1013 (37.2 trillion)†.

• Erythrocytes (Red blood cells: 2.63 × 1013 ), 26.3 trillion in all, transport
oxygen from the lungs to the tissue.
• Dermal fibroblasts (Skin): 1.85 × 1012 .
• Endothelial cells (Vessels): 2.54 × 1012
• Neurons (Nervous system): 1.00 × 1011
• Heart muscle cells (Heart): 2.00 × 109

†Eva Bianconi, Allison Piovesan, Federica Facchin, Alina Beraudi, Raffaella Casadei, Flavia
Frabetti, Lorenza Vitale, Maria Chiara Pelleri, Simone Tassani, Francesco Piva, Soledad Perez-
Amodio, Pierluigi Strippoli & Silvia Canaider, "An estimation of the number of cells in the human
body", Annals of Human Biology, Volume 40, Issue 6, pages 463-471 (2013)

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 Cells as the living units of the body

8
 Cells as the living units of the body

9
 Cells as the living units of the body

10
11
• The cell contains highly organized physical structure, many of
which are called organelles. Reconstruction of a typical cell
showing the internal organelles in the cytoplasm and in the
nucleus:

Cell
membrane
 The Cell Membrane:
• Cell membrane is 6 to 10 nm thick and consists of the phospholipid bilayer with
embedded proteins.
• It is a biological membrane that separates the interior of all cells from the outside
environment (separates the intracellular fluid from extracellular fluid).
• It forms a barrier to the free diffusion of ions, and control the concentration of
electrolytes inside of the cell.

Extracellular Fluid

Intracellular Fluid (Cytoplasm)

Electrophysiology is the study of the electrical properties of biological cells and tissues.
12
Approximate chemical compositions of extra- and intra-cellular fluids:

Ionic concentration inside & outside of a typical mammalian cell

NOTE:
- Large quantities of sodium (Na+) and only small quantities of potassium (K+) in
extracellular fluid; Exactly the opposite is true of the intracellular fluid.
- Large quantities of chloride (Cl-) in extracellular fluid and little in intracellular fluid.
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 The cell membrane properties:

• Lipid bilayer which is not miscible with extra- or intracellular fluid.

• Large number of protein molecules floating in the lipid and many penetrating all the way through
to form the various channels through which ions diffuse cross membranes.
• A channel maybe open or closed as a result of conformational changes in the channel proteins.
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 The cell membrane properties:

A simplified structure of membrane

• Transport pathways through the cell membrane, and the basic mechanisms of transport

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 The cell membrane properties:
Gating of Protein channels

1. Voltage gating: the molecular conformation of the gate responds to the change of electrical
potential (field) across the membrane.
Example:
Sodium channels remain closed when there is a strong negative charge on the inside of the cell
membrane. The gate will open when the negative charge is lost. The tremendous sodium ions
diffuse into the cell. This is a basic cause of action potentials in nerves that are responsible for
nerve signals.

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 The cell membrane properties:
Gating of Protein channels

2. Ligand gating: Some protein channel open due

to binding with other molecules. The substances
that binds is called ligand

Example: Acetylcholine opens the channel

providing a pore about 0.65 nm that allows the
molecules and ions smaller than this size to pass
through. This gate is important in the
transmission of signal from one nerve cell to
other cells (nerve, muscle etc.)

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 The cell membrane properties:
Gating of Protein channels

3. Facilitated diffusion: also called carrier-

mediated diffusion. Some substances usually
can not pass through the membrane without
help from a specific carrier protein. The
carrier facilitate the diffusion of the substance
to the other side.

Figure on the left:

Comparison of simple diffusion and facilitated
diffusion through a membrane. This illustrates
that facilitated diffusion approaches a
maximum rate called the Vmax
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 The cell membrane properties:
Selective permeability of different protein channels

Na+ channels: K+ channels:

• 0.3 ~ 0.5 nm in size • 0.3 nm in size.
• inner surfaces are strongly • not charged.
negatively charged to pull the • Hydrated potassium is smaller than
sodium ion from the water hydrated sodium.
(hydrated Na+).

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 2.1 The membrane Potential of a Resting Cell
• When a cell is in a "resting" or equilibrium state, the potential across the membrane has a
constant value, referred to as the "resting potential"
• Large difference in ionic concentrations inside and outside of the cell. Unequal distribution
of ions or ionic gradient gives rise to an electrical potential across the membrane.

? Driving force to keep the ionic gradient?

A: a Na-K pump that continuously transport Na+
out of the cell and K+ into the cell ( ratio =
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three Na+ : two K+)
 2.1 The membrane Potential of a Resting Cell
Nernst Equation: Calculation of Resting Potential
• Given the knowledge of the concentrations of various ions and permeability of the
membrane to the ions, it is possible to calculate the resting potential of cell in much the
same way the equilibrium potential across the PN junction is calculated.
• Basic idea is to balance the flux result from diffusion and electrical field (drift) across the
membrane.

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 2.1 The membrane Potential of a Resting Cell
Nernst Equation: Calculation of Resting Potential
• Given the knowledge of the concentrations of various ions and permeability of the
membrane to the ions, it is possible to calculate the resting potential of cell in much the
same way the equilibrium potential across the PN junction is calculated.
• Basic idea is to balance the flux result from diffusion and electrical field (drift)
across the membrane.
Fick' s Law (diffusion)
• If there is a high concentration of particles in one
region that are free to move, they will flow in a
direction to equalize the concentration through
the region.

For diffusion of positively charged particles:

Current density:
𝑑𝑑 𝐶𝐶
𝐽𝐽 = −𝐷𝐷 (A/unit area, A/m2)
𝑑𝑑𝑑𝑑

where [C] is the ion concentration (mol/liter); D is

the diffusion coefficient[(liter � A)/(mol � m)]; x An ionic concentration as a function of position.
is the position.
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 2.1 The membrane Potential of a Resting Cell
Nernst Equation: Calculation of Resting Potential
• Given the knowledge of the concentrations of various ions and permeability of the
membrane to the ions, it is possible to calculate the resting potential of cell in much the
same way the equilibrium potential across the PN junction is calculated.
• Basic idea is to balance the flux result from diffusion and electrical field (drift)
across the membrane.

Particle drift:
Charges particles in an electrical field will
move under the force of electrical
attraction and repulsion.

Drift current density:

𝑑𝑑𝑑𝑑
𝐽𝐽𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑 = −𝜇𝜇𝜇𝜇 𝐶𝐶
𝑑𝑑𝑑𝑑
where 𝜇𝜇 is the mobility (𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙𝑙 � 𝐴𝐴/(𝑉𝑉 �
𝑚𝑚𝑚𝑚𝑚𝑚 � 𝑚𝑚); Z is the valence; E is the
electrical field intensity (V/m); [C] is the
concentration of ions (mol/liter).

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 2.1 The membrane Potential of a Resting Cell
Nernst Equation: Calculation of Resting Potential
• Given the knowledge of the concentrations of various ions and permeability of the
membrane to the ions, it is possible to calculate the resting potential of cell in much the
same way the equilibrium potential across the PN junction is calculated.
• Basic idea is to balance the flux result from diffusion and electrical field (drift)
across the membrane.

Two physical constants, mobility µ and the diffusion coefficient D, are related to each
other by the Einstein relationship:
𝐷𝐷 𝑘𝑘𝑘𝑘
=
𝜇𝜇 𝑞𝑞
where k is the Boltzmann ' s constant, q is the charge, and T is the absolute temperature.

The Fick' s law, drift equation and Einstein relationship can be used to
derive the membrane potential in biological cells.

𝑑𝑑 𝐶𝐶 𝑑𝑑𝑑𝑑 𝐷𝐷 𝑘𝑘𝑘𝑘
𝐽𝐽 = −𝐷𝐷 𝐽𝐽𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑 = −𝜇𝜇𝜇𝜇 𝐶𝐶 =
𝑑𝑑𝑑𝑑 𝑑𝑑𝑑𝑑 𝜇𝜇 𝑞𝑞
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 2.1 The membrane Potential of a Resting Cell
Nernst Equation: Calculation of Resting Potential
• Consider a simple system consisting of a membrane that separates electrolytes
containing different concentrations of potassium ions:

148 mM Vm 5 mM The diffusion current density or flux:

𝑑𝑑 𝐾𝐾 +
𝐽𝐽𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑 = −𝐷𝐷𝑘𝑘
𝑑𝑑𝑑𝑑

If the electrical field inside the membrane is

constant, then, 𝑃𝑃𝑘𝑘 = 𝐷𝐷𝑘𝑘 ⁄𝑤𝑤, where 𝑃𝑃𝑘𝑘 is
the permeability and 𝑤𝑤 is the width or
thickness of the membrane.

The drift current:

𝑑𝑑𝑉𝑉𝑚𝑚 +
= 𝜇𝜇𝑘𝑘 𝑧𝑧𝐸𝐸� 𝐾𝐾 + = −𝜇𝜇𝑘𝑘 𝑧𝑧
𝐽𝐽𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑 𝐾𝐾
𝑑𝑑𝑑𝑑
where 𝑉𝑉𝑚𝑚 is the potential across the
membrane.

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 2.1 The membrane Potential of a Resting Cell
Nernst Equation: Calculation of Resting Potential
• If the system is in equilibrium, no net current flows across the membrane and the
diffusion and drift currents must be equal,
𝐽𝐽𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢 = 𝐽𝐽𝑑𝑑𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟
148 mM Vm 5 mM
𝑑𝑑𝑉𝑉𝑚𝑚 + 𝑑𝑑 𝐾𝐾 +
−𝜇𝜇𝑘𝑘 𝑧𝑧 𝐾𝐾 = −𝐷𝐷𝑘𝑘
𝑑𝑑𝑑𝑑 𝑑𝑑𝑑𝑑
𝑥𝑥2 𝑥𝑥2
𝑑𝑑𝑉𝑉𝑚𝑚 𝐷𝐷𝑘𝑘 1 𝑑𝑑 𝐾𝐾 +
� 𝑑𝑑𝑑𝑑 = � + 𝑑𝑑𝑑𝑑
𝑑𝑑𝑑𝑑 𝑧𝑧𝜇𝜇𝑘𝑘 𝐾𝐾 𝑑𝑑𝑑𝑑
𝑥𝑥1 𝑥𝑥1

−𝐷𝐷𝑘𝑘 𝐾𝐾+ 2
𝑉𝑉𝑚𝑚 = 𝑉𝑉2 -𝑉𝑉1 = 𝑙𝑙𝑙𝑙 +
𝑧𝑧𝜇𝜇𝑘𝑘 𝐾𝐾 1

Applying the Einstein relationship:

−𝑘𝑘𝑘𝑘 𝐾𝐾 + 2
𝑉𝑉𝑚𝑚 = 𝑙𝑙𝑙𝑙 +
𝑧𝑧𝑞𝑞 𝐾𝐾 1

x1 x2 This equation, which is applicable to K+

(z=1) or any ion, is the Nernst Equation.
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 2.1 The membrane Potential of a Resting Cell
Goldman Equation: Calculation of Resting Potential
In the more realistic case of a cell membrane
that separates intracellular and extracellular
fluids containing many different ions, a more
general equation can be derived by imposing
the following conditions:
• All of the drift and diffusion currents
caused by the different ionic gradient sun
to zero.
• Space-charge neutrality (i.e., the
numbers of positive and negative ions in
a given volume are, on average, equal at
all times)
𝐽𝐽𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢 = 𝐽𝐽𝑑𝑑𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟
The Goldman Equation:
𝑘𝑘𝑘𝑘 𝑃𝑃𝑘𝑘 𝐾𝐾 + 𝑖𝑖 + 𝑃𝑃𝑁𝑁𝑁𝑁 𝑁𝑁𝑁𝑁+ 𝑖𝑖 + 𝑃𝑃𝐶𝐶𝐶𝐶 𝐶𝐶𝐶𝐶− 𝑜𝑜 𝐷𝐷𝑖𝑖
𝑉𝑉𝑚𝑚 = 𝑉𝑉𝑜𝑜 −𝑉𝑉𝑖𝑖 = − ln 𝑃𝑃𝑖𝑖 =
𝑞𝑞 𝑃𝑃𝑘𝑘 𝐾𝐾 + 𝑜𝑜 + 𝑃𝑃𝑁𝑁𝑁𝑁 𝑁𝑁𝑁𝑁+ 𝑜𝑜 + 𝑃𝑃𝐶𝐶𝐶𝐶 𝐶𝐶𝐶𝐶− 𝑖𝑖 𝑤𝑤
where the variables 𝑃𝑃𝑏𝑏 , 𝑃𝑃𝑁𝑁𝑁𝑁 and 𝑃𝑃𝐶𝐶𝐶𝐶 are the permeability coefficients of the
27 membrane for potassium, sodium and chloride ions.
𝐷𝐷𝑖𝑖 is the diffusion coefficient and 𝑤𝑤 is the thickness of membrane.
 2.1 The membrane Potential of a Resting Cell
Goldman Equation: Calculation of Resting Potential
The Goldman Equation:
𝑘𝑘𝑘𝑘 𝑃𝑃𝑘𝑘 𝐾𝐾 + 𝑖𝑖 + 𝑃𝑃𝑁𝑁𝑁𝑁 𝑁𝑁𝑁𝑁+ 𝑖𝑖 + 𝑃𝑃𝐶𝐶𝐶𝐶 𝐶𝐶𝐶𝐶− 𝑜𝑜 𝐷𝐷𝑖𝑖
𝑉𝑉𝑚𝑚 = 𝑉𝑉𝑜𝑜 −𝑉𝑉𝑖𝑖 = − ln 𝑃𝑃𝑖𝑖 =
𝑞𝑞 𝑃𝑃𝑘𝑘 𝐾𝐾 + 𝑜𝑜 + 𝑃𝑃𝑁𝑁𝑁𝑁 𝑁𝑁𝑁𝑁+ 𝑜𝑜 + 𝑃𝑃𝐶𝐶𝐶𝐶 𝐶𝐶𝐶𝐶− 𝑖𝑖 𝑤𝑤

• These values, when substituted in Goldman equation, yield 𝑉𝑉𝑚𝑚 ≈ − 82 𝑚𝑚𝑚𝑚.

• Experimentally, the resting potentials of variety of muscle and nerve cells have been
found to be in the range of -60 to -90 mV.

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 2.1 The membrane Potential of a Resting Cell
Goldman Equation: Calculation of Resting Potential
The Goldman Equation:
𝑘𝑘𝑘𝑘 𝑃𝑃𝑘𝑘 𝐾𝐾 + 𝑖𝑖 + 𝑃𝑃𝑁𝑁𝑁𝑁 𝑁𝑁𝑁𝑁+ 𝑖𝑖 + 𝑃𝑃𝐶𝐶𝐶𝐶 𝐶𝐶𝐶𝐶− 𝑜𝑜 𝐷𝐷𝑖𝑖
𝑉𝑉𝑚𝑚 = 𝑉𝑉𝑜𝑜 −𝑉𝑉𝑖𝑖 = − ln 𝑃𝑃𝑖𝑖 =
𝑞𝑞 𝑃𝑃𝑘𝑘 𝐾𝐾 + 𝑜𝑜 + 𝑃𝑃𝑁𝑁𝑁𝑁 𝑁𝑁𝑁𝑁+ 𝑜𝑜 + 𝑃𝑃𝐶𝐶𝐶𝐶 𝐶𝐶𝐶𝐶− 𝑖𝑖 𝑤𝑤

Potassium ions have the dominant role in determining the resting potential in nerve and muscle cell.
To verify this, we can neglect all contribution from other ions and calculate the membrane potential:

−𝑘𝑘𝑘𝑘 𝐾𝐾 + 𝑖𝑖 153
∆𝑉𝑉 = 𝑙𝑙𝑙𝑙 + = −27𝑚𝑚𝑚𝑚 𝑙𝑙𝑙𝑙 ≈ −98𝑚𝑚𝑚𝑚
𝑞𝑞 𝐾𝐾 𝑜𝑜 4

This calculation yields similar value as the Goldman Equation.

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 2.2 The action Potential:
• The membrane Potential of cell (nerve or muscle) in its excited state

Types of nerve cells

(neurons)

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 2.2 The action Potential:
• The membrane Potential of cell (nerve or muscle) in its excited State

Types of muscle fibers

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 2.2 The action Potential:
• The membrane Potential of cell in its excited state

Nerve and muscle cells have the unique property that, when stimulated, their membranes undergo a
cyclic change in their permeability to Na+ and K+ ions which momentarily reverses the membrane
potential.
→ generating pusatile signal called Action Potential

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 2.2 The action Potential:
• The membrane Potential of cell in its excited State

Triggering Mechanisms:
• Sensory cells, which are actually specialized nerve cells, are
sensitive to externally applied stimuli, such as light, heat or
movement.
• Most of other cells (nerve, muscle) are stimulated internally by
electrical signal (potential change) and chemical signal (ligand)
generated by sensory cells.
• Regardless the origin of the stimulation, the action of potential is
the consequence of sudden change of permeability of membrane
to Na+ ions.

A Positive feedback cycle:

The increased permeability of membrane to sodium ion is caused by that Vm becomes less
negative. The sodium ions rush into the cell cause the membrane potential more positive, this
makes the sodium channel open further more.
• generate a sharp electrical signal.
33 • causes membrane potential to move rapidly toward the sodium Nernst potential.
 2.2 The action Potential:
• The membrane Potential of cell in its excited State

Brakes:
The K+ channels respond the voltage change slower than
Na+ channels. However, after a round 1 ms the potential
change is applied, the potassium channels start to open
and balance the ion flux. The membrane potential starts
to get back to the normal (resting membrane potential).

Na+/K+ Pump:
• A type of pumping protein (enzyme) that uses ATP
(Adenosine Triphosphate) as energy source to keep
the gradient.
• Binding 3-sodium and 2-potassium ions → reacts
with ATP to obtain energy conformation change
release ions.
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 2.2 The action Potential:
• The membrane Potential of cell in its excited State

Regenerative nature of the action potential:

Action potential is an all-or-none phenomenon. This means the cycle that generates the
action potential always goes to completion once that it is triggered. The signal remains
the same from cell to cell.
35
 2.2 The action Potential:
• The membrane Potential of cell in its excited State

Na+/K+ pump

Regenerative nature of the action potential:

Action potential is an all-or-none phenomenon. This means the cycle that generates the
action potential always goes to completion once that it is triggered. The signal remains
the same from cell to cell.
36
 2.2 The action Potential:
• The membrane Potential of cell in its excited State

Regenerative nature of the action potential:

Action potential is an all-or-none phenomenon. This means the cycle that generates the
action potential always goes to completion once that it is triggered. The signal remains
the same from cell to cell.
37
 Action potential and muscle contraction:
• In muscle fiber, where cells are situated in an orderly arrangement, the tissue contracts and
becomes shorter in length after some delay following a depolarization or action potential
passing through.

38
 Action potential and muscle contraction:
• In muscle fiber, where cells are situated in an orderly arrangement, the tissue contracts and
becomes shorter in length after some delay following a depolarization or action potential
passing through.

39
 Action potential and muscle contraction:

• In muscle fiber, where cells are situated in an orderly arrangement, the tissue contracts and
becomes shorter in length after some delay following a depolarization or action potential
passing through.

40
 Action potential and muscle contraction:
• In muscle fiber, where cells are situated in an orderly arrangement, the tissue contracts and
becomes shorter in length after some delay following a depolarization or action potential
passing through.

41
 An electrical model of the nerve cell

Variable- resistor
𝑔𝑔𝑛𝑛 𝑡𝑡, 𝑉𝑉 Na+/K+
𝐶𝐶𝑚𝑚 Pump
𝑉𝑉𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟

A simplified Hodgkin–Huxley model treats each component of an excitable cell as an

electrical element.
• The lipid bilayer is represented as a capacitance (Cm).
• Voltage-gated ion channels are represented by electrical conductances, 𝑔𝑔𝑛𝑛 𝑡𝑡, 𝑉𝑉 ,
where n is the specific ion channel (Na+, K+, Cl+) that depend on both voltage
and time.
• The electrochemical gradients driving the flow of ions are represented by voltage
sources (𝐸𝐸𝑛𝑛 ) whose voltages are determined by the ratio of the intra- and
extracellular concentrations of the ionic species of interest.
• Ion pumps are represented by current sources.
• The membrane potential is denoted by 𝑉𝑉𝑚𝑚 .
42
 An electrical model of the nerve cell

Nerve cell

Nerve fiber

Propagation of action potential

43
 2.3 Propagation of Action Potential
• Experimental observations:

Arrangement for recording

action potentials from the
giant fibers in the nerve cord
of the earth worm.

A B
Biphasic action potential

44
 2.3 Propagation of Action Potential

Conductive fiber

45
Cylinder model of nerve or muscle fiber
 2.3 Propagation of Action Potential

Propagation of action potentials in both

directions along a conductive fiber.
• Action potential occurs at one spot on the
membrane → exciting adjacent portions
of membrane, resulting in propagation of
the action potential.

Cylinder model of nerve fiber

A normal resting nerve fiber:

46
 2.3 Propagation of Action Potential
Nerve fiber

47
 2.3 Propagation of Action Potential
A: a normal resting nerve fiber
B: a nerve fiber that has been excited in its
midportion → suddenly increased permeability
to sodium
C and D: spreading of action potential
• Arrows indicate the “local circuit” of current
flow between the depolarized and the
adjacent resting membrane areas –
• Kirchhoff ’s current law 𝑰𝑰𝒆𝒆𝒆𝒆 ≡ 𝑰𝑰𝒊𝒊𝒊𝒊

Iex

− − − − − − − − − − − −++++++++++++
++++++++++++ − − − − − − − − − − − −
Depolarized Iin Polarized
++++++++++++++ − − − − − − − − − −
− − − − − − − − − − − − − −++++++++++
Action
potential
48
 2.3 Propagation of Action Potential

• Kirchhoff ’s current law: 𝑰𝑰𝒆𝒆𝒆𝒆 ≡ 𝑰𝑰𝒊𝒊𝒊𝒊 ≡ 𝑰𝑰𝒐𝒐 ≡ 𝑰𝑰𝒊𝒊

Trans-membrane currents

Iex -Ii Io
Io
− − − − − − − − − − − −++++++++++++ − − − − − − − − − − − − − − ++++++++++++++
++++++++++++ − − − − − − − − − − − − ++++++++++++++ − − − − − − − − − − − − − −
Depolarized Ii Iin Polarized
Depolarized Polarized
++++++++++++++ − − − − − − − − − −
− − − − − − − − − − − − − −++++++++++
Action
potential

Action
potential
Trans-membrane Trans-membrane
A propagating action potential can be described current Sink current Source
as a traveling current sink-source pair -Ii Io
separated with distance d.
d
49
 2.3 Propagation of Action Potential
• Model of propagating action potential: a traveling current sink-source pair

t=t1
-Ii Io
x
x1

t=t2
-Ii Io
x
x2

t=t3
-Ii Io
x
x3
𝒙𝒙𝟐𝟐 −𝒙𝒙𝟏𝟏
Velocity of traveling current sink-source pair: 𝑉𝑉 =
50 𝒕𝒕𝟐𝟐 −𝒕𝒕𝟏𝟏
 2.3 Propagation of Action Potential
Action
potential 𝑉𝑉
Ohm’s law: 𝐼𝐼 = = 𝜎𝜎𝜎𝜎
Current Sink Current Source 𝑅𝑅
-Ii Io where 𝜎𝜎 = 𝜋𝜋𝑎𝑎2 𝜎𝜎𝑖𝑖
d
2
𝜕𝜕𝜕𝜕
• How to determine the values Differential form: 𝐼𝐼 = 𝜋𝜋𝑎𝑎 𝜎𝜎𝑖𝑖
of current sink and source? 𝜕𝜕𝑥𝑥

Cylindrical tube model

Intracellular current:
𝑑𝑑𝑑𝑑
𝝓𝝓𝒊𝒊 𝒙𝒙, 𝒕𝒕 𝐼𝐼𝑖𝑖 𝑥𝑥, 𝑡𝑡
x
2a

𝑰𝑰𝒊𝒊
2
𝜕𝜕𝜙𝜙𝑖𝑖 𝑥𝑥, 𝑡𝑡
= 𝜋𝜋𝑎𝑎 𝜎𝜎𝑖𝑖
𝜕𝜕𝑥𝑥
𝐼𝐼𝑖𝑖 𝑥𝑥, 𝑡𝑡
51
 2.3 Propagation of Action Potential

𝑥𝑥 𝑥𝑥 + ∆𝑥𝑥 Intracellular current:

𝜕𝜕𝜙𝜙𝑖𝑖 𝑥𝑥, 𝑡𝑡
𝐼𝐼𝑖𝑖 𝑥𝑥 + ∆𝑥𝑥, 𝑡𝑡
2a

𝐼𝐼𝑖𝑖 𝑥𝑥, 𝑡𝑡 𝐼𝐼𝑖𝑖 𝑥𝑥, 𝑡𝑡 = 𝜋𝜋𝑎𝑎2 𝜎𝜎𝑖𝑖

𝜕𝜕𝑥𝑥

𝐼𝐼𝑚𝑚 Trans-membrane current at x

Kirchhoff ’s current law: 𝐼𝐼𝑖𝑖 𝑥𝑥, 𝑡𝑡 = 𝐼𝐼𝑚𝑚 + 𝐼𝐼𝑖𝑖 𝑥𝑥 + ∆𝑥𝑥, 𝑡𝑡

𝑜𝑜𝑜𝑜 𝐼𝐼𝑖𝑖 𝑥𝑥 − 𝐼𝐼𝑖𝑖 𝑥𝑥 + ∆𝑥𝑥 = 𝐼𝐼𝑚𝑚

Taylor’s expansion: 𝐼𝐼𝑖𝑖 𝑥𝑥 + ∆𝑥𝑥 = 𝐼𝐼𝑖𝑖 𝑥𝑥 − 𝐼𝐼𝑖𝑖′ 𝑥𝑥 ∆𝑥𝑥 + ⋯

𝜕𝜕 2 𝜙𝜙
𝑖𝑖
𝐼𝐼𝑚𝑚 = ∆𝐼𝐼𝑖𝑖 𝑥𝑥, 𝑡𝑡 ≈ 𝐼𝐼𝑖𝑖′ 𝑥𝑥, 𝑡𝑡 ∆𝑥𝑥 = 𝜋𝜋𝑎𝑎2 𝜎𝜎𝑖𝑖 ∆𝑥𝑥
𝜕𝜕𝑥𝑥 2
52
 2.3 Propagation of Action Potential
𝜕𝜕 2 𝜙𝜙
𝑖𝑖
Trans-membrane current at 𝑥𝑥: 𝐼𝐼𝑚𝑚 = ∆𝐼𝐼𝑖𝑖 𝑥𝑥, 𝑡𝑡 ≈ 𝐼𝐼𝑖𝑖′ 𝑥𝑥, 𝑡𝑡 ∆𝑥𝑥 = 𝜋𝜋𝑎𝑎2 𝜎𝜎𝑖𝑖 ∆𝑥𝑥
𝜕𝜕𝑥𝑥 2
𝑥𝑥0 +∞
𝐼𝐼𝑜𝑜 = � 𝐼𝐼𝑚𝑚 𝑑𝑑𝑑𝑑
−∆𝑥𝑥 ∆𝑥𝑥 𝑥𝑥0

− − − − − − − − − − − − − − ++++++++++++++
++++++++++++++ − − − − − − − − − − − − − −
x 𝑥𝑥𝑜𝑜
𝐼𝐼𝑖𝑖 = � 𝐼𝐼𝑚𝑚 𝑑𝑑𝑑𝑑
−∞

±∆𝑥𝑥 𝑖𝑖𝑖𝑖 𝑡𝑡𝑡𝑡𝑡 𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟 𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 𝑡𝑡𝑡𝑡𝑡 𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜 𝑜𝑜𝑜𝑜 𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖 𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐. 𝐼𝐼𝑜𝑜 = 𝐼𝐼𝑖𝑖
If a single fiber is immersed in an extensive
Current Sink Current Source conducting medium, the extracellular
-Ii Io potential 𝜙𝜙𝑒𝑒 is small (≈ 0). So that
membrane potential is about equal to 𝜙𝜙𝑖𝑖 .
d
𝑉𝑉𝑚𝑚 = 𝜙𝜙𝑖𝑖 −𝜙𝜙𝑒𝑒 ≈ 𝜙𝜙𝑖𝑖

2 𝜙𝜙 2 𝑉𝑉
𝜕𝜕 𝑖𝑖 𝜕𝜕 𝑚𝑚
𝐼𝐼𝑜𝑜,𝑖𝑖 = 𝜋𝜋𝑎𝑎2 𝜎𝜎𝑖𝑖 � 2 𝑑𝑑𝑥𝑥 𝐼𝐼 = 𝜋𝜋𝑎𝑎2 𝜎𝜎𝑖𝑖 � 𝑑𝑑𝑥𝑥
±∆𝑥𝑥 𝜕𝜕𝑥𝑥 ±∆𝑥𝑥 𝜕𝜕𝑥𝑥
2
53
2.4 Measurement of Propagating Action Potential
• Potential signal of a single current source
Φ𝑒𝑒 𝑅𝑅 𝑥𝑥, 𝑧𝑧
𝑧𝑧 Electrostatics (Handout#3 and #3a)
• the study of forces between charges, as
described by Coulomb's Law
𝑅𝑅
𝑟𝑟⃑ 1 𝐼𝐼
Φ𝑒𝑒 𝑅𝑅 =
4𝜋𝜋𝜎𝜎𝑒𝑒 𝑟𝑟
𝑥𝑥 1�
∆𝑥𝑥 𝐼𝐼 𝑥𝑥′, 𝑡𝑡 𝑤𝑤𝑤𝑤𝑤𝑤𝑤𝑤𝑤 𝑟𝑟 = 𝑥𝑥 − 𝑥𝑥 ′ 2 + 𝑧𝑧 2 2
Current Source

𝜕𝜕 2 𝑉𝑉
𝑚𝑚
Consider Action Potential: 𝐼𝐼𝑖𝑖,𝑜𝑜 = 𝜋𝜋𝑎𝑎2 𝜎𝜎𝑖𝑖 � 2
𝑑𝑑𝑥𝑥𝑥
∆𝑥𝑥 𝜕𝜕𝑥𝑥′
∆𝑥𝑥 𝑖𝑖𝑖𝑖 𝑡𝑡𝑡𝑡𝑡 𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟 𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 𝑡𝑡𝑡𝑡𝑡 𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜 𝑜𝑜𝑜𝑜 𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖 𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐.

1 𝐼𝐼𝑖𝑖,𝑜𝑜 𝑎𝑎2 𝜎𝜎𝑖𝑖 1 𝜕𝜕 2 𝑉𝑉𝑚𝑚 ′

Φ𝑒𝑒 𝑅𝑅 = = � 2 𝑑𝑑𝑥𝑥
4𝜋𝜋𝜎𝜎𝑒𝑒 𝑟𝑟 4 𝜎𝜎𝑒𝑒 𝑟𝑟 ∆𝑥𝑥 𝜕𝜕𝑥𝑥 ′
2.4 Measurement of Propagating Action Potential
• Potential signal of a single current source

𝑎𝑎2 𝜎𝜎𝑖𝑖 1 𝜕𝜕 2 𝑉𝑉𝑚𝑚 ′

𝑧𝑧
Φ𝑒𝑒 𝑅𝑅 = � � �� 2 𝑑𝑑𝑥𝑥
4 𝜎𝜎𝑒𝑒 𝑟𝑟 ∆𝑥𝑥 𝜕𝜕𝑥𝑥 ′

𝑅𝑅 The equation describes a general case

𝑟𝑟⃑
• The potential is proportional to the square
of fiber size
𝑥𝑥 • The potential is proportional to the ratio of
∆𝑥𝑥 𝐼𝐼 𝑥𝑥′, 𝑡𝑡
conductivity of intracellular vs.
Current Source extracellular fluid
• The potential decreases as 1/r when the
source of the current is further away;
2 • The observed potential increases when the
2 𝜎𝜎𝑖𝑖 1 𝜕𝜕 𝑉𝑉𝑚𝑚 𝜕𝜕2 𝑉𝑉𝑚𝑚
Φ𝑒𝑒 ∝ 𝑎𝑎 , , , 2 membrane current is greater ( 𝜕𝜕𝑥𝑥 2 is
𝜎𝜎𝑒𝑒 𝑟𝑟 𝜕𝜕𝑥𝑥 greater).
 2.4 Measurement of Propagating Action Potential
• Current sink-source pair: an Electric Dipole
Electrostatics (Handout#3 and #3a): A current source-sink pair separated by a
• An electric dipole is a separation of positive and short distance d is called a dipole too.
negative charges.
• The electrostatic potential and electric field due Φ𝑒𝑒 𝑟𝑟⃑
to an electric dipole:

𝑟𝑟0
𝑟𝑟⃑ 𝑟𝑟1

𝜃𝜃
𝑥𝑥
-I d I

Treat it as two lumped source:

1 −𝐼𝐼 𝐼𝐼
Φ𝑒𝑒 = +
• The electric field is a measure of force per unit 4𝜋𝜋𝜎𝜎𝑒𝑒 𝑟𝑟0 𝑟𝑟1
charge; the electric potential is a measure of 𝑟𝑟0 , 𝑟𝑟1 𝑎𝑎𝑎𝑎𝑎𝑎 𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑 𝑓𝑓𝑓𝑓𝑓𝑓𝑓𝑓 𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠
energy per unit charge. 𝑡𝑡𝑡𝑡 𝑡𝑡𝑡𝑡𝑡 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 𝑎𝑎𝑎𝑎𝑎𝑎 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠
 2.4 Measurement of Propagating Action Potential
• Current sink-source pair: an Electric Dipole

𝐼𝐼 1 Electrostatics (Handout#3 and #3a):

Φ𝑒𝑒 𝑟𝑟⃑ = 𝛻𝛻 � 𝑑𝑑⃑
4𝜋𝜋𝜎𝜎𝑒𝑒 𝑟𝑟 Φ𝑒𝑒 𝑟𝑟⃑
Electric dipole moment, 𝑃𝑃 = 𝐼𝐼 𝑑𝑑⃗
where 𝑑𝑑⃗ is the displacement vector pointing
from the current sink to the source. The
𝑟𝑟0 electric dipole moment vector 𝑃𝑃 also points
𝑟𝑟⃑ 𝑟𝑟1 from the sink to the source.
𝑷𝑷 𝜃𝜃
𝑥𝑥 • It is a measure of the separation of positive and
-I 𝑑𝑑⃗ I negative electrical charges within a system, that
is, a measure of the system's overall polarity.
• The electric field strength of the dipole is
𝐼𝐼𝐼𝐼 𝑟𝑟̂ � 𝑎𝑎�𝑑𝑑 𝑃𝑃 𝑟𝑟̂ � 𝑎𝑎�𝑑𝑑 proportional to the magnitude of dipole moment.
𝛷𝛷𝑒𝑒 𝑟𝑟⃑ = =
4𝜋𝜋𝜎𝜎𝑒𝑒 𝑟𝑟 2 4𝜋𝜋𝜎𝜎𝑒𝑒 𝑟𝑟 2

1 𝑃𝑃 𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 𝑎𝑎2 𝜎𝜎𝑖𝑖 𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 𝜕𝜕 2 𝑉𝑉𝑚𝑚 Action Potential can be

𝛷𝛷𝑒𝑒 𝑟𝑟⃑ = 2
= 2
𝑑𝑑 � 2
𝑑𝑑𝑑𝑑 measured REMOTELY!
4𝜋𝜋𝜎𝜎𝑒𝑒 𝑟𝑟 4 𝜎𝜎𝑒𝑒 𝑟𝑟 𝛥𝛥𝑥𝑥 𝜕𝜕𝑥𝑥
 2.4 Measurement of Propagating Action Potential
• Current sink-source pair: an Electric Dipole

𝑎𝑎2 𝜎𝜎𝑖𝑖 𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 𝜕𝜕 2 𝑉𝑉𝑚𝑚

𝛷𝛷𝑒𝑒 𝑟𝑟⃑ = � � 2
� 𝑑𝑑 � � 2
𝑑𝑑𝑑𝑑
4 𝜎𝜎𝑒𝑒 𝑟𝑟 𝛥𝛥𝑥𝑥 𝜕𝜕𝑥𝑥

𝑟𝑟0
𝑟𝑟⃑ 𝑟𝑟1 • The potential is proportional to the square of
fiber size
𝜃𝜃
𝑥𝑥 • The potential is proportional to the ratio of
-I 𝑑𝑑⃗ I conductivity of intracellular vs. extracellular
fluid
• The potential decreases as 1/𝑟𝑟 2 when the
source of the current is further away; and is a
function of measurement angle θ (∝ 𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐).
• Of course, the observed potential is
determined by the action potential itself.
 2.4 Measurement of Propagating Action Potential
• Estimation of observed potential

Example: 𝑎𝑎2 𝜎𝜎𝑖𝑖 𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 𝜕𝜕 2 𝑉𝑉𝑚𝑚

𝛷𝛷𝑒𝑒 𝑟𝑟⃑ = 2
𝑑𝑑 � 2
𝑑𝑑𝑑𝑑
For a large nerve immersed in a 4 𝜎𝜎𝑒𝑒 𝑟𝑟 𝛥𝛥𝑥𝑥 𝜕𝜕𝑥𝑥
large tank of saline (salt water ):
𝑑𝑑 = 𝑥𝑥2 − 𝑥𝑥1
𝜎𝜎𝑖𝑖
≈ 0.2
𝜎𝜎𝑒𝑒 𝜕𝜕𝜕𝜕𝑖𝑖 𝜕𝜕𝜕𝜕𝑚𝑚
2 2
𝜙𝜙𝑒𝑒 is small 𝐼𝐼 = 𝜋𝜋𝑎𝑎 𝜎𝜎𝑖𝑖 ≈ 𝜋𝜋𝑎𝑎 𝜎𝜎𝑖𝑖
𝑎𝑎 ≈ 50𝜇𝜇𝜇𝜇 10−6 𝑚𝑚 𝜕𝜕𝜕𝜕 𝜕𝜕𝜕𝜕

𝑟𝑟 ≈ 10 𝑚𝑚𝑚𝑚
𝜕𝜕𝜕𝜕𝑚𝑚
d is small ≈ 𝑉𝑉𝑚𝑚 𝑥𝑥2 − 𝑉𝑉𝑚𝑚 𝑥𝑥1 ⁄ 𝑥𝑥2 − 𝑥𝑥1
𝜕𝜕𝜕𝜕
∆𝑉𝑉𝑚𝑚 ≈ 100 𝑚𝑚𝑚𝑚
𝑎𝑎2 𝜎𝜎𝑖𝑖 𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 𝜕𝜕𝜕𝜕𝑚𝑚
𝜙𝜙𝑒𝑒 ≈ 𝑑𝑑
4 𝜎𝜎𝑒𝑒 𝑟𝑟 2 𝜕𝜕𝜕𝜕
𝛷𝛷𝑒𝑒 𝑟𝑟⃑ =?
𝑎𝑎2 𝜎𝜎𝑖𝑖 𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐
𝜙𝜙𝑒𝑒 ≈ 𝑉𝑉𝑚𝑚 𝑥𝑥2 − 𝑉𝑉𝑚𝑚 𝑥𝑥1
4 𝜎𝜎𝑒𝑒 𝑟𝑟 2
 2.4 Measurement of Propagating Action Potential
• Estimation of observed potential

𝑎𝑎2 𝜎𝜎𝑖𝑖 𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐

Example: 𝜙𝜙𝑒𝑒 ≈ 𝑉𝑉𝑚𝑚 𝑥𝑥2 − 𝑉𝑉𝑚𝑚 𝑥𝑥1
4 𝜎𝜎𝑒𝑒 𝑟𝑟 2
For a large nerve immersed in a
large tank of saline (salt water ):
𝑎𝑎2 𝜎𝜎𝑖𝑖 𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐
𝜎𝜎𝑖𝑖
𝜙𝜙𝑒𝑒 ≈ ∆𝑉𝑉𝑚𝑚
4 𝜎𝜎𝑒𝑒 𝑟𝑟 2
≈ 0.2
𝜎𝜎𝑒𝑒

𝑎𝑎 ≈ 50𝜇𝜇𝜇𝜇 10−6 𝑚𝑚 𝐹𝐹𝐹𝐹𝐹𝐹 𝑡𝑡𝑡𝑡𝑡 𝑏𝑏𝑏𝑏𝑏𝑏𝑏𝑏 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠, 𝜃𝜃 = 0

𝑟𝑟 ≈ 10 𝑚𝑚𝑚𝑚
𝛷𝛷𝑒𝑒 𝑟𝑟⃑ ~ 0.5𝜇𝜇𝜇𝜇 ‼!
∆𝑉𝑉𝑚𝑚 ≈ 100 𝑚𝑚𝑚𝑚

Extremely difficult to detect.

𝛷𝛷𝑒𝑒 𝑟𝑟⃑ =?
 2.4 Measurement of Propagating Action Potential

Summary of Important Concepts

Potentials measured exterior to a nerve or muscle fiber:

• can be calculated by modeling depolarized regions as an
equivalent electric dipoles.

• depend on the differences between the membrane

potential 𝑉𝑉𝑚𝑚 measured at points along the fiber.

• are generally much smaller than 𝑉𝑉𝑚𝑚 .

• Alternatively equation to calculate observed potential:

𝑃𝑃 𝑟𝑟̂ � 𝑎𝑎�𝑑𝑑 1 𝑟𝑟𝑟𝑟̂ � 𝑃𝑃 𝑎𝑎�𝑑𝑑
𝛷𝛷𝑒𝑒 𝑟𝑟⃑ = = �
4𝜋𝜋𝜎𝜎𝑒𝑒 𝑟𝑟 2 4𝜋𝜋𝜎𝜎𝑒𝑒 𝑟𝑟 3

1 𝑃𝑃 𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 1 𝑟𝑟⃗ � 𝑃𝑃
𝛷𝛷𝑒𝑒 𝑟𝑟⃑ = 𝛷𝛷𝑒𝑒 𝑟𝑟⃑ = � 3
4𝜋𝜋𝜎𝜎𝑒𝑒 𝑟𝑟 2 4𝜋𝜋𝜎𝜎𝑒𝑒 𝑟𝑟