Chapter4

Membrane Potentials and Action

Potentials
 Membrane Potentials and Action Potentials
* Electrical potentials exist across membranes of all cells.
* The inside surface of the membrane is negatively charged
in relation to the outside and the outside surface is
positively charged in relation to the inside.
* Membrane potential is measured
by small pipette filled with an
electrolyte solution (Silver-silver
chloride solution) and inserted into
fiber interior. Another electrode
called indifferent electrode is
placed in extracellular fluid and
potential difference between the
inside and outside of the fiber is
measured using a voltmeter.
* Membrane potential across the nerve fiber at rest was found to
be −90 mV and is called resting membrane potential (RMP) i.e.
The potential inside the fiber is 90 mV more negative than the
potential in the extracellular fluid on the outside of the fiber.
Resting membrane potential
* Definition: RMP is a potential across the nerve fiber at rest and
it is equal −90 mV.
* Origin of RMP:
1. Potassium leak channel:
- It leaks potassium ions to the outside even
in a resting cell.
- It may also leak sodium ions to the inside,
but are about 100 times more permeable to
potassium than to sodium.
- It contributes to -86 mV of the RMP
2. Na/K pump
- Continually pumps three sodium ions to outside for every
two potassium ions to cell inside leading to continual loss of
positive charges from inside, creating an additional degree
of negativity (contributes to about −4 mV additional) on the
inside.
- Therefore, K leak channels and Na/K pump give a net
membrane potential of −90 mV.
 Local potential (Graded potential)
* Definition: Local potential is a local change in the membrane potential
that can not spread along the nerve fiber membrane.
* Generation of local potential:
When a subthreshold stimulus is applied to a nerve fiber
conformational changes in activation gates of small number of voltage-
gated sodium channels flipping gates all the way to the open position
membrane sodium ions pour inward through channels membrane
potential becomes less negative and rising from RMP of −90 mV to
somewhere between −70 and −50 mV returns to RMP without
spreading along the nerve fiber membrane i.e. local potential.
 Action potential
* Definition: Action potential is a rapid change in the membrane potential
that spread rapidly along the nerve fiber membrane.
* Generation of action potential:
When a threshold stimulus is applied to a nerve fiber the following
successive stages of action potential occur:
1. Depolarization stage:
Membrane potential becomes less negative than during the resting state
rising from −90 mV toward zero reaches a voltage −70 to −50 mV
sudden conformational change
in activation gates of large number of
voltage-gated sodium channels
flipping gates all the way to
open position sodium ions pour
inward through channels, increasing
membrane permeability to sodium
as much as 500- 5000 fold.
- The membrane potential at which most of voltage-gated
sodium channels open (about −65 mV) is called threshold
potential or firing level.
- In large nerve fibers, the great excess of positive sodium ions
moving to the inside causes the membrane potential to
“overshoot” beyond the zero level and to become positive.
- At a membrane potential +35 mV, the inactivation gate of
voltage-gated sodium channels closes about 1 msec after the
activation gate opens.

2. Repolarization stage:
When voltage-gated sodium channels close conformational
opening of the gate of voltage gated potassium increased
potassium diffusion outward through the channel return
membrane potential to −90 mV in about 2 msec i.e. full
recovery of RMP.
3. Hyperpolarization stage:
- Hyperpolarization stage is caused by continual opening or
delayed closure of voltage-gated potassium channels rendering
the membrane potential to exceed the RMP i.e. more negative
inside the fiber.
- Hyperpolarization stage is called after potential and it lasts
for about 4 msec.

* A Positive-Feedback Cycle Opens Sodium Channels

Stimulation of a nerve fiber rising membrane potential
from −90 mV towards Zero level opening of many voltage-
gated sodium channels rapid inflow of sodium ions
further rise in membrane potential opening more
voltage-gated sodium channels and so on (Positive-feedback
cycle).
* Re-establishment of RMP: Performed by Na/K pump (recharging
of the nerve) and required energy that derived from ATP.
* Refractory periods of Action Potential
1. Absolute Refractory Period (ARP):
- ARP is the period at which the nerve fiber does not respond
whatever was the strength of the stimulus.
- ARP coincides with depolarization stage of action potential.
2. Relative Refractory Period (RRP):
- RRP is the period at which the nerve fiber responds at the
condition that the stimulus was strong i.e. maximum stimulus.
- RRP coincides with repolarization stage of action potential.
* All-or-Nothing Principle: means that once an action potential has
been elicited, the depolarization process travels over the entire
membrane. Therefore, action potential does not change in shape
and amplitude on propagation across a nerve fiber.
 Propagation of Action Potential
* Action potential is conducted across a nerve fiber in two ways:
1. Point to point conduction: Occurs in unmyelinated nerve fibers
Mechanism:
The action potential is generated in
nerve fiber segment in response to
threshold stimulus attraction
between positive and negative
charges of the adjacent segment
local circuit currents (sink
current) opening of voltage-
gated sodium channels of the
adjacent segment depolarization
and generation of action potential in
the adjacent segment and so on.
2. Saltatory conduction: Occurs in myelinated nerve fibers
Mechanism:
The action potential is generated in
nerve fiber at node of Ranvier
(formed by multiple layers of
Schwann cell rotating around the
axon and containing sphingomyelin)
in response to threshold stimulus
attraction between positive
and negative charges of the
adjacent node local circuit
currents (sink current) opening of voltage-gated sodium
channels of the adjacent segment depolarization and
generation of action potential in the adjacent node and so on.
Saltatory conduction is 5-50 times faster than point to point
conduction.
 Plateau of Action potential in heart muscle fibers
* The plateau of action potential in heart muscle lasts for 0.2-0.3
second and causes contraction of heart muscle to last for this same
long period.
* The plateau of action potential in heart muscle coincides with ARP
which is a safety factor for the heart.
* Ion channels responsible for plateau in
heart muscle include:
1. In depolarization stage:
A. Voltage-gated sodium channels, fast
opening channels: allow sodium ions to
enter the fiber and cause spike portion
of action potential.
B. Voltage-gated calcium channels, L-type calcium channels, slow
opening channels: allows calcium ions to enter the fiber and cause
most of the plateau of action potential.
2. In repolarization stage:
A. Voltage-gated potassium channels, slow opening channels: allow
potassium ions to exit from the fiber and partly responsible for the
plateau in being delay the return of the membrane potential toward
RMP.

Rhythmicity of Some Excitable Tissues—Repetitive Discharge

* Rhythmicity or repetitive discharges occurs in:
1. Heart e.g. rhythmical heart beat.
2. Smooth muscle e.g. rhythmical peristalsis of intestine.
3. Neurons e.g. rhythmical control of breathing.
* rhythmicity occur when the membrane is permeable enough to
sodium or calcium ions through L-type calcium channels to allow
automatic membrane depolarization.
* The RMP in rhythmical control center of the heart is only −60 to −70
mV, which is not enough negative voltage to keep sodium and calcium
channels totally closed.
* Therefore, the following sequence occurs:
Some sodium and calcium ions flow inward increases
membrane voltage in positive direction further increases in
membrane permeability depolarization repolarization
Hyperpolarization which gradually disappears, allowing the
membrane potential to increase up to the threshold for
depolarization again and a new action potential occurs
spontaneously (rhythmicity).