PHYSIOLOGY

2. THE NERVE I

Dr. Nadia Yassin

 MEMBRANE POTENTIALS
There is a marked difference in composition of intracellular & extra-
cellular fluid (ICF & ECF).
Intracellular Extracellular
Fluid (ICF) Fluid (ECF)
Main Cations K+ Na+
Main Anions proteins, phosphates Cl-, HCO3-

These variations create an electrical potential (= voltage difference)

between the inside & outside of the cell membrane. It is called the
membrane potential.

Forms of Membrane Potentials in Nerves:

A. Under resting conditions: Resting Membrane Potential (RMP)
B. On stimulation with an inadequate (= subthreshold) stimulus:
Graded Potential = Local Response
C. On stimulation with an adequate (= threshold) stimulus:
2
Action Potential
 A. Resting Membrane Potential (RMP)
Definition: It is the potential of the membrane at rest.
Measurement of RMP:
- If 2 microelectrodes placed on the surface of a nerve fiber are
connected to a voltmeter  no potential difference is observed.
- If 1 microelectrode is inserted into the nerve fiber, while the other
remains outside  a steady
potential difference of 70 mV
is recorded with the inside being
negative with respect to the surface.
This is the RMP of the nerve fiber.
- By convention, the potential out-
side is defined as zero.
 The potential difference is
expressed as a negative value
 -70 mV. 3
 A. RMP (cont.)
Magnitude of RMP:
- At rest, all cells have a potential difference across their cell
membrane,
with the inside being –ve to the outside = “polarized state”.
- The magnitude of RMP varies from 5-100 mV, depending on cell type:
[high in excitable tissues, low in non-excitable tissues]: e.g.
 In large neurons & skeletal muscle fibers: - 90 mV
 In medium-sized neurons: - 70 mV
 In non-excitable tissues, e.g., RBCs: - 20 to - 40 mV
Cause of RMP:
- There is a tiny excess of –ve ions inside
the cell & tiny excess of +ve ions outside.
- Excess –ve ions inside are attracted to
excess +ve ions outside.  They form a
thin layer at the inner & outer surfaces
of the membrane, while the bulk of ICF
& ECF is neutral. 4
 A. RMP - Cause of RMP (cont.)
N.B. The membrane of nerves contains 2 types of ion channels:
1. Non-gated channels: They are always open.
2. Gated channels: At rest they are closed! They open & close in
response to specific signals: electrical, mechanical or chemical.
In RMP only non-gated channels play a significant role!!!
N.B. 2 forces act on ions in a solution:
1. Concentration gradient: Ions diffuse from an area of high conc. to an
area of low conc.
2. Electric gradient: Ions are attracted by opposite charges & are
repelled by ions of the same charge.

Unequal
distribution
of diffusible ions
across the
cell membrane
5
 A. RMP - Cause of RMP (cont.)
1. Selective Permeability of Cell Membrane:
The membrane permeability is restricted.
The membrane is:
- totally resistant to passage of large protein
anions (A-)
- extremely resistant to passage of Na+ ions
(few Na+ channels)
- moderately resistant to passage of K+ ions
(50-100 x more than Na+ channels)
- slightly resistant to passage of Cl- ions.

a PROTEIN IONS (A-): They are trapped inside the cells. They are
called “fixed anions”.
b. Cl- IONS: : They can pass easily into the cell, but are repelled by
inner negativity.
6
N.B. Of the diffusible ions, Na & K play the most important role.
+ +
 A. RMP - Cause of RMP (cont.)
1. Selective Permeability of Cell Membrane: (cont.)
c. K+ IONS:
- According to concentration gradient:
K+ conc. is very high inside the cell
compared to outside
 tendency of K+ to diffuse out.
- According to electrical gradient:
Inside is –ve compared to outside
 tendency of K+ to diffuse in.
- Permeability:
There is moderate permeability for K+.

 At rest, there is continuous diffusion of a

some K+ ions out of cell with concentration
gradient & against electric gradient.
7
 A. RMP - Cause of RMP (cont.)
1. Selective Permeability of Cell Membrane: (cont.)
d. Na+ IONS:
- According to concentration gradient:
Na+ conc. is very high outside the cell
compared to inside
 tendency of Na+ to diffuse in.
- According to electrical gradient:
Inside is –ve compared to outside
 tendency of Na+ to diffuse in.
- Permeability:
There is low permeability for Na+.

 At rest, there is continuous diffusion of

a few Na+ ions into cell with concentration & electric gradients.

 At rest there is net diffusion of more K+ ions

out of cell than Na+ ions into cell.
8
 A. RMP - Cause of RMP (cont.)
2. Sodium-Potassium Pump:
- Loss of conc. gradients is ultimately prevented by Na+-K+ pump.
- It has: 3 binding sites for Na+ on the inside
2 binding sites for K+ on the outside.
It carries 3 Na+ ions out and 2 K+ ions into the cell.
- It moves both ions against their conc. gradients. Therefore it is an
active transport system that requires E.
- The pump is an enzyme, Na+-K+ ATPase,
that derives its E from hydrolysis of ATP.
- It is also called an “electrogenic pump”
as it transports more positive ions out of
the cell than into it, thus contributing a
little to the RMP.
9
 A. RMP - Calculations
The role of diffusible ions (Na+, K+ & Cl-) can be analyzed mathematically:
1. Calculation of Equilibrium Potential by Nernst Equation:
- This equation considers the forces acting on each individual ion on
its own, i.e., it is based on the membrane being permeable to only one
ion at a time.
- It allows us to calculate the equilibrium potential for each of the
diffusible ions, i.e., the electrical potential that is necessary to balance
the concentration gradient across the membrane, so that the net flux
(= diffusion) of this ion is zero.

E = 60 x log [Co] / [Ci] at 37ºC

E = equilibrium pot., [Co] = conc. of ion outside, [Ci] = conc. of ion inside
10
60 = a constant value that takes various factors into account.
 A. RMP – Calculations (cont.)
1. Calculation of Equilibrium Pot. by Nernst Eq.: (cont.)
A. Calculation for K+: (permeab. of membr. to Na+ & Cl- is taken as zero)
EK = 60 x log [K+o]/[K+i] = - 90 mV
Since EK is not at RMP (-70 mV), K+ constantly diffuse out of the cell.
B. Calculation for Na+: (perm. of membr. to K+ & Cl- is taken as zero)
ENa = 60 x log [Na+o]/[Na+i] = + 60 mV.
Since ENa is not at RMP, Na+ constantly diffuse into the cell.
Because the membrane permeability at rest is so much higher to K+
than to Na+, the RMP is primarily near the equilibrium potential of K+ (EK)
and not near the equilibrium potential of Na+ (ENa).

2. Calculation of RMP by Goldman Equation:

It gives an accurate calculation of RMP.
This equation takes into consideration (all at the same time):
- the distribution of Na+, K+ & Cl-
- the membrane permeability to these ions. 11
 TERMINOLOGY
- Polarized state: at rest the inside of the membrane is –ve to the outside.
- Depolarization: the membrane potential is less –ve than RMP.
- Overshoot (= reversal of polarity): the inside of the membrane becomes
+ve to the outside.
- Repolarization: the depolarized membrane returns to RMP.
- Hyperpolarization: membrane potential is more –ve than RMP.
Such changes in membrane potential occur as a result of changes in
permeability of the membrane to ions (due to opening of gated channels).

12
B. GRADED POTENTIAL = LOCAL RESPONSE
Definition:
- It is a change in membrane potential following a subthreshold stimulus.
- It is confined to a relatively small area of the cell membrane: “local
response”.
- It involves gated channels.

Characteristics:
1. Depolarization or hyperpolarization:
With stimulation, certain gated channels are activated & opened,
resulting in influx or efflux of ions for which the channel is specific:
 Opening of Na+ channels  influx of Na+ into nerve fiber   negativity
in this area = depolarization.
 Opening of K+ channels  efflux of K+ out of nerve fiber   negativity
in this area = hyperpolarization. 13
B. GRADED POTENTIAL = LOCAL RESPONSE
(cont.)
Characteristics: (cont.)
2. Graded:
- The magnitude of the local response is proportional to the intensity of
the stimulus.
- The stronger the stimulus, the greater the number of opened channels.

N.B. The intensity of the stimulus must be subthreshold (<10 mV).

14
B.GRADED POTENTIAL = LOCAL RESPONSE (cont.)
Characteristics: (cont.)
3. Spreads by passive local
current flow:
- When a local response occurs,
charges flow passively between the
place of origin of the response & the adjacent regions of the membrane,
which are still at RMP.
- E.g., if a small region of the membrane has become depolarized:
 inside the cell has become +ve  these +ve charges will flow away from
depolarized area toward adjacent more –ve resting membrane  adjacent area
becomes +ve, while previously depolarized area becomes –ve once more.
 outside the cell has become –ve  +ve charges from adjacent resting areas
will flow toward the less +ve region created by depolarization  adjacent areas
become –ve, while previously depolarized area becomes +ve once more.
 The surplus ions (+ve inside & -ve outside) will radiate out in all
directions, depolarizing adjacent areas of the cell membrane.
 As the depolarization spreads like a wave, it leaves behind it a
membrane that was formerly depolarized & quickly returns to RMP. 15
B.GRADED POTENTIAL = LOCAL RESPONSE (cont.)
Characteristics: (cont.)
4. Decremental:
- As the depolarization wave moves
along the membrane, it quickly loses
intensity & dies out.

- This is mainly due to leakage of

K+ ions out through non-gated
channels.

- Because the current dissipates

quickly & is short lived, graded
potentials can only act as signals
over short distances (few mm)
 called ”local response”.
16
B.GRADED POTENTIAL = LOCAL RESPONSE (cont.)
Characteristics: (cont.)
5. Summation:
- If additional subthreshold stimuli occur before the local response dies
away, they are added to the depolarization created by the first stimulus.
- There are 2 types:
1. Temporal Summation:
where several successive
stimuli are applied rapidly
after each other.
2. Spatial Summation:
where several simultaneous
stimuli are applied in close
proximity to each other.

N.B. Graded potentials usually occur in dendrites & soma. Their

purpose is to drive axon hillock to threshold so that an action
potential is generated. 17