The student will be able to: (MUST KNOW)

• Understand the concept of resting membrane

potential (RMP).

• Explain the mechanism of genesis and

maintenance of RMP.
 BASIC CONCEPTS OF PHYSICS OF
MEMBRANE POTENTIAL

• An electrical potential difference exists across the

membrane of all living cells with the inside being
negative in relation to the outside.
• This potential difference is called membrane potential
as ions arrange themselves along the outer and inner
surfaces of the cell membrane

• At resting state of the cell, the membrane potential is

called resting membrane potential (RMP)
Special features of RMP are:
• In a nerve cell, the RMP is –70 mV.
• When the neuron is stimulated, membrane potential
changes and inside of the cell becomes positive due to
depolarization. The membrane potential during this
state of activation is called action potential.
• RMP plays an important role in deciding the degree
and duration of action potential, as the RMP is the
level from where the phase of depolarization starts.
• In some tissues like visceral smooth muscles, RMP is
not stable (fluctuates).
 Cause for RMP
• Membrane potential is mainly due to distribution of
ions across the cell membrane, which results mainly
from the selective permeability of the cell membrane
to various ions at rest.

• However, this is influenced by various forces acting on

the ion distribution
• Understanding the following concepts of
physics help the students to learn the
physiology of RMP.
1. Selective permeability of the cell
membrane to various ions
2. Gibbs–Donnan equilibrium
3. Nernst equation
4. Goldmann-Hodgkin equation
Selective Permeability of the Membrane

• The cell membrane is selectively permeable to ions

and other solute particles. Some ions are highly
permeable, some are less permeable and others are
impermeable.

• The permeability mainly depends on the molecular

weight and the radius of ions in their hydrated form
Selective Permeability of the Membrane

• Though the ions like Na+, K+, Cl– and HCO3– are
diffusible through the membrane, the permeability is
more for K+.

• The permeability for K+ is 500 to 1000 times greater

than that for Na+ for its effective radius.

• The membrane is practically impermeable to

intracellular proteins and organic phosphates.
 Gibbs-Donnan Membrane Equilibrium

• When two solutions containing ions are separated by

a semipermeable membrane, at equilibrium, each
solution will be electrically neutral.
• The total quantity of cations will be equal to total
quantity of anions. Also, the product of diffusible ions
on one side of the membrane will be equal to product
of diffusible ions on the other side of the membrane.
• This is called Gibbs-Donnan membrane equilibrium.
For example, two solutions A and B containing sodium
and chloride ions are separated by a semipermeable
membrane.
• However, when a non-diffusible ions ‘X’ is added on one side,
then as per Gibbs’-Donnan equilibrium principle, the
distribution of diffusible ions will change to maintain
electroneutrality of both sides
 Donnan Effect

• Presence of non-diffusible ion on one side of the

membrane affects the distribution of other ions to
which membrane is permeable.
• This results in asymmetrical distribution of ions across
the cell membrane.
• This is called Donnan effect.
 Nernst Equation

• In accordance with Gibbs’-Donnan equilibrium,

asymmetrical distribution of diffusible ions occurs
across the cell membrane with more cation (K+)
present inside.

• Therefore, K+ will try to diffuse into the ECF from ICF,

which is opposed by the electrical gradient, created by
presence of non-diffusible anions inside the cell.
• Thus, finally equilibrium is reached between the
concentration gradient and the electrical gradient
resulting in diffusion potential (equilibrium potential)
across the cell membrane.
• The degree of this equilibrium potential is
determined by Nernst equation:

• Equilibrium potential for

– Sodium is 60 mV
– Potassium is -90 mV
 Goldman-Hodgkin-Katz Equation
• The magnitude of the membrane potential at any
given time depends on the distribution of Na+, K+ and
Cl– and on the permeability of each of these ions. The
role of different ions in the generation of membrane
potential is accurately described by Goldman-
Hodgkin-Katz (GHK) equation or also called
Goldman’s constant field equation.
Importance of Goldman constant field equation

[Link] ions that generate membrane potentials in

nerve and muscle fibers are sodium, potassium and
chloride. The voltage of membrane potential is
determined by the concentration gradient of each of
these ions.

2. The relativity of importance of each ion in

determination of the voltage depends upon the
membrane permeability of individual ion.
3. Cation concentration from inside the membrane to
outside is responsible for electronegativity inside the
membrane. Due to concentration gradient, cations
diffuse to outside of the cell leaving the non-diffusible
anions inside the cell.
 GENESIS OF RESTING MEMBRANE
POTENTIAL (RMP)

Resting membrane potential is the membrane potential

at rest. RMP is the electrical potential difference existing
just across the plasma membrane of a resting cell.
The RMP is created due to following factors.
• 1. Differential permeability of the plasma membrane
to different cations and anions
• 2. Differential distribution of ions across the plasma
membrane due to differential permeability and
Donnan effect
• 3. Na+-K+ pump
 Causes of RMP are:
1. Permeability of the membrane to K + :
Normally, K+ is more inside and less outside the cell
Therefore, a concentration gradient exists for K + from inside
to outside that facilitates K + to diffuse out of the cell.
At rest, permeability of the membrane to K + is higher than
any other ion.
Therefore, K+ easily diffuses out of the cell, though this is
opposed by the electrical gradient. As, K+ is the major
intracellular cation, its diffusion creates negativity inside the
cell.
The permeability of the membrane to K+ is the major cause of
RMP
2. Relative impermeability of the membrane of
resting cells to Na+:
• At rest, ECF Na+ is more than the ICF Na+.
• Therefore, there is a concentration gradient for Na+
from outside to inside, for which Na+ diffuses into the
cell.
• However, at rest membrane is less permeable to Na+
(Fig. 7.3) than to K+.
• Therefore, K+ exit is not balanced by Na+ entry (more
K+ goes out). Hence, interior of the cell remains
relatively negative.
3. Permeability to anions:
• Exit of more cations from the cell should be
accompanied by proportionate exit of anion to
maintain electroneutrality.

• However, exit of K+ (the cation) is not accompanied by

exit of same amount of anions as permeability of
anions at rest is also not same as that of K+.
Therefore, more negative ion remains inside
4. Role of Na+-K+ pump:
• The role of Na+ -K+ pump is to maintain RMP
rather than to generate it.
• Na+ -K+ pump also contributes to the genesis of
RMP (the contribution is about ̶ 4mV), as it is an
electrogenic pump. It pumps out three Na+ for
two K+ to come in.
• It pumps more cations out of the cell and less
into the cell.
• Thus, less cations are taken inside, which in other
words, a relatively negativity is created inside.
 Maintenance of RMP
• K+ diffusing out of the cell and Na+ diffusing into the
cell will come to halt once the concentration gradient
ceases to exist for both the ions.
• That does not happen, as Na+-K+ ATPase helps in
building the concentration gradient.

• It serves to pump back the Na+ that diffuses into the

cell and K+ that diffuses out of the cell. Thus, Na+ -K+
pump plays an important role in maintaining RMP
1. Most diffusible ion in an excitable tissue is
A. Sodium B. Chloride C. Phosphate D Potassium

2. Nernst potential for potassium is

B. -90mV B.-70 mV C. +70 mV D. +90 mV

3. Equilibrium potential for sodium is

C. +60mV B.+90 mV C. +70 mV D. -90 mV

4. RMP is mainly due to permeability of membrane to

A. Sodium B. Chloride C. Magnesium D Potassium
5. Potassium has greater permeability through a semipermeable
membrane because
A. Size of molecule is large B. Hydrated K+ is small
C. Atomic weight of Na+ is less D. Concentration gradient

6. The RMP of a nerve fiber is equal to equilibrium potential of----

 Action potential
• Ability of the cells to generate action
potential in their membrane is known as
excitability

• Nerve (and muscle) is a highly excitable

tissue, which can be stimulated by
electrical, chemical and mechanical forms of
energy

• The message transmission occurs by means

of generation and propagation of the
electrical signals in the axon from one end
Action potential (AP)
Definition: The rapid depolarization and
repolarization process generates an voltage pulse
peak when stimulated by a threshold stimulus is
called action potential or nerve impulse.

• Brief sequence of changes which occur in the

resting membrane potential when stimulated by a
threshold stimulus

• Duration: 1 msec

• Amplitude: 100mV (–70 to +35 mV)

 Action potential
Types of Stimuli-

• At –55 mV, the neuron starts generating action

potentials.
• This is termed as firing or discharge of the neuron
and
–55 mV is known as the firing level or threshold level.
• Threshold stimulus: The lowest strength of stimulus
that elicits an action potential.
• Subthreshold stimuli: The stimuli less in strength
than the threshold
• Suprathreshold stimuli: The stimuli higher in
strength than the threshold
• Subliminal stimulus: A sensory stimulus below a
person’s threshold for conscious perception.
 Phases of Action potential
1. Stimulus Artifact
2. Latent period
3. Beginning of
depolarization
4. Firing level or threshold
5. Over shoot
6. Repolarization
7. Spike potentials (rapid rising
& falling phase)
8. After-depolarization
9. After-hyperpolarization
 Phases of Action potential
Stimulus Artifact
Is recorded as mild deflection in base line as soon as
the stimulus is applied
Occurs due to the leakage of current from the
stimulating electrode to the recording electrode
Latent Period
Time interval between the application of stimulus and
the onset of action potential
It depends upon -
Distance between stimulation point & recording point
Velocity of action potential
 Phases of Action potential
Beginning of depolarization-
• In the axon at resting state, only leaky
channels are open.
• The early part of local response is due to
entry of sodium ions through the leaky
channels.
• When the change in membrane potential
is
about +7 mV (-63mV), few of the voltage-
gated
Na+ channels begin to open.
 Phases of Action potential
Depolarization-Rapid rise
At -55mV (threshold level/ firing level), there is
simultaneous opening of a large number of the
voltage-gated Na+ channels,
The membrane permeability increases to Na+ several
hundredfold.
Depolarization is due to opening of voltage-gated Na+
channels
In the stimulated region of membrane, at threshold,
the number of Na+ channels that have already
opened, cause simultaneous activation of huge
number of Na+ channels (autoactivation), which
occurs very rapidly
 Phases of Action potential
Depolarization-
• This leads to massive influx of sodium ions
producing a swift, large and steep
depolarization, changing the membrane
potential to +35 mV (Overshoot)
• Hodgkins cycle-The opening of few Na+
channels leading to further opening of other
Na + channels
• This is an example of positive feedback
control in which a stimulus triggering an
event further facilitates the process.
 Phases of Action potential
Repolarization-
• After the over shoot potential reverses and
falls rapidly toward the resting level.
• due to opening of voltage-gated K+
channels causing efflux of K+ and closure
of voltage-gated Na+ channels
• Voltage-gated K+ channels are sensitive to
depolarization that opens the voltage-
gated Na+ channels but they open more
slowly.
 Phases of Action potential
Repolarization-
• Factors favoring K+ efflux:
• The K+ concentration is much higher inside
the cell (Chemical gradient)
• At the peak of the action potential, outside
of the membrane is negative in comparison
to inside, which is +35 mV positive
(Electrical gradient)
• Rapid falling phase repolarization is brought
about by decline in sodium influx together
with increase in potassium efflux
 Phases of Action potential
After Depolarization-
Due to slower efflux of potassium ions that
considerably decreases the rate of
repolarization and makes the repolarization
curve oblique (less steep)

After Hyperpolarization-
After reaching the resting level the potential
further falls as some potassium efflux
continues and becomes more negative
Action potential
Activity after AP-
• At the end of AP-more sodium and less
potassium inside the cell.
• The ionic composition is restored by
increased activity of the Na+-K+ ATPase.
• The Na+ and K+ ions movements during an AP
produces a negligible change in the intracellular ionic
concentration. However, if this imbalance were not
taken care of, following repeated generation of action
potentials, slowly the concentration gradients of
sodium and potassium across the membrane will
cease to exist
Ionic basis of Action potential
 Effects of Extracellular Ionic Changes

1. Decreased extracellular Na+ concentration, the

amplitude of the AP becomes smaller than usual
because the concentration gradient for Na+ that
drives sodium into the cell is reduced.
2. Increased extracellular Na+ concentration, the
amplitude of the AP may increase.
3. Decreased extracellular K+ concentration, the
membrane potential becomes more negative as the
resting K+ efflux is favored by the increased
concentration gradient across the membrane.
4 Increased extracellular K+ concentration, the
membrane potential come closer to the firing level
and the membrane becomes more excitable.
 Effects of Extracellular Ionic Changes

5. Decreased extracellular Ca2+ concentration-

electrical potential difference across the
membrane is decreased and also makes the
voltage gated sodium channels easily open
• therefore RMP comes closer to the firing level, so
that, the magnitude of depolarization needed to
reach the firing level is less.
• Hence, decrease in extracellular Ca++
concentration increases the excitability of the
tissue, as observed in hypocalcemic tetany,
occurring in hypoparathyroidism.
6. Increased extracellular Ca2+ concentration, the
RMP goes away from the firing level decreasing
the tissue excitability.
PY3.1. Describe the structure and functions of a neuron and
neuroglia. Discuss Nerve Growth Factor

[Link] the parts of a neuron and list their functions.

[Link] the various types of glial cells and their functions
[Link] the formation and chemical nature of myelin
sheath
[Link] the conduction of impulses in myelinated and
unmyelinated nerve fibers and their significance
[Link] orthograde and retrograde transmission
[Link] the different nerve growth factors and cytokines
Formation of myelin sheath
 Chemical nature of myelin sheath
• Chemical nature-Myelin contains protein, lipids
(cholesterol, phospholipid and glycosphingolipids )
and water

• Schwann cells play a vital role in axon regeneration.

• Impaired Schwann cell functioning is mainly
associated with demyelinating diseases, such as
multiple sclerosis.
• Diabetic neuropathy is another disorder associated
with Schwann cell damage in both sensory and motor
nerves.
[Link]

[Link]
Conduction of impulses in myelinated and unmyelinated
nerve fibers and their significance
Orthograde and Retrograde transmission
Axoplasmic transport refers to the movement of material
within the axon. Organelles, vesicles, and proteins can be
moved from the cell body to the terminal via anterograde
transport. This is done by microtubules which run the
length of the axon and provide the cytoskeleton tracks
necessary for the transportation of materials. Kinesin is a
motor protein that uses ATP and is used in anterograde
transport of materials.

Transport from the terminal to the cell body via retrograde

transport.
Dynein is another motor protein which uses ATP, but is
used in retrograde transport.
 Growth of Neurons
Various factors affect neuronal development,
growth and survival

I. Neurotrophins:
II. Other Growth factors
- Cilliary NTF
- Glial cell-line derived NTF
- Leukemia inhibitory factor
- FGF, PDGF, TGF, IGF-1
 Neurotrophins

• They are trophic proteins to the neurons, as

they promote nerve growth and survival.
• They are produced by the nerves, muscles,
glands and astrocytes.
Known neurotrophins are:
1. Nerve growth factor (NGF),
2. Brain-derived neurotrophic factor (BDNF),
3. Neurotrophin – 3 (NT-3),
4. Neurotrophin 4/5
 Nerve Growth Factor

• First neurotrophin to be identified

• Promotes the growth and survival of
sympathetic nerves and some sensory nerves.
• An autocrine survival factor for memory B
lymphocytes.
• Found in high concentration in the saliva of
male mice
• Decreases apoptosis of neurons by acting
through tyrosine kinase A receptor.
 Neurotrophins

Brain-derived Neurotrophic Factor (BDNF)

• Promotes growth of peripheral sensory nerves.
• Acts through tyrosine kinase A.

Neurotrophin3
• Promotes growth of cutaneous mechanoreceptors.
• Acts through tyrosine kinase A, B and C.

Neurotrophins 4 &5
• Act through tyrosine kinase B, its exact function is not
known.