PHYSIOLOGY COURSE

MMP 1215

DR. VELU M. RACHEL

ACTION POTENTIALS
 ACTION POTENTIALS

• Resting membrane potential describes the

steady state of the cell, which is a dynamic
process that is balanced by ion leakage and
ion pumping.
• Without any outside influence, it will not
change. To get an electrical signal started, the
membrane potential has to change.
 ACTION POTENTIALS

• Transient changes in the membrane potential

from its resting level produce electric signals.
• Such changes are the most important way that
nerve cells process and transmit information.
 ACTION POTENTIALS con’t…

• These signals occur in two forms:

Graded potentials and Action potentials.
• Graded potentials are important in signaling over
short distances,
• Whereas action potentials are the long-distance
signals of nerve and muscle membranes
• Therefore an action potential describes the electrical
signal that is generated when a stimulus causes a
change in membrane potential above threshold
 ACTION POTENTIALS con’t…

• And this is for the purpose of transmitting impulses

down an axon or from one neuron to another or
from one muscle fiber to another.
• Nerve, muscle, some endocrine, immune and
reproductive cells have plasma membranes capable
of producing action potentials
• Their membranes are called excitable membranes
hence excitable cells.
 ACTION POTENTIALS con’t…

• All cells are capable of conducting graded potentials

only excitable cells can conduct action potentials.
• Nerve impulses are transmitted in form of action
potentials.
• These are basically rapid changes in the membrane’s
resting potential.
 ACTION POTENTIALS con’t…

• An action potential generally begins with a sudden

change from the normal resting potential to a
positive membrane potential and then back to the
resting potential.
• Therefore an Action Potential is a rapid change in the
membrane potential during which the membrane
rapidly depolarizes and repolarizes.
 ACTION POTENTIALS con’t…

• Let take an example of a channel opening for Na+ in

the membrane.
• Because the concentration of Na+ is higher outside
the cell than inside the cell by a factor of 10, ions will
rush into the cell that are driven largely by the
concentration gradient.
• Because sodium is a positively charged ion, it will
change the relative voltage immediately inside the
cell relative to immediately outside.
 ACTION POTENTIALS con’t…

• The resting potential is the state of the membrane at

a voltage of -70 mV, so the sodium cation entering
the cell will cause it to become less negative.
• This is known as depolarization, meaning the
membrane potential moves toward zero.
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• The concentration gradient for Na+ is so strong that it

will continue to enter the cell even after the
membrane potential has become zero, so that the
voltage immediately around the pore begins to
become positive.
• The electrical gradient also plays a role, as negative
proteins below the membrane attract the sodium
ion.
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• The membrane potential will reach +30 mV by the

time sodium has entered the cell.
• As the membrane potential reaches +30 mV, other
voltage-gated channels are opening in the
membrane.
• These channels are specific for the potassium ion.
 ACTION POTENTIALS con’t…

• A concentration gradient acts on K+, as well. As K+

starts to leave the cell, taking a positive charge with
it, the membrane potential begins to move back
toward its resting voltage. This is called
repolarization,
• meaning that the membrane voltage moves back
toward the -70 mV value of the resting membrane
potential.
 ACTION POTENTIALS con’t…

• In neurons, the potential reverses and the

membrane becomes positive inside.
• APs provide means by which long-distance
transmission of information through the
nervous system can take place
 Stages of an Action potential

• As noted earlier action potentials results from

a transient change in the membrane’s ion
permeability, which allows selected ions to
move down their concentration gradients

• Therefore the stages of an action potential

include :
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 The Resting Stage
• In the resting state, the open channels in the plasma
membrane are predominantly those that are
permeable to potassium (and chloride) ions. Very
few sodium-ion channels are open.
• The membrane is said to be “polarized’ because of
the very large negative membrane potential that is
present.
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Depolarization Phase
• The depolarizing phase of the action potential
is due to the opening of voltage-gated sodium
channels, which increases the membrane
permeability to sodium ions several
hundredfold.
• This allows more sodium ions to move into the
cell.
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• During this period, therefore, more positive charge
enters the cell in the form of sodium ions than
leaves in the form of potassium ions, and the
membrane depolarizes.
• It may even overshoot, becoming positive on the
inside and negative on the outside of the
membrane.
• Depolarization makes the membrane potential less
negative (the cell interior becomes less negative).
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Repolarization stage
• At this stage the sodium channels begin to close and
potassium channels open much more.
• The diffusion of potassium ions to the outside brings
the membrane to its normal negative resting
potential.
• This is because potassium diffusion out of the cell is
then much greater than the sodium diffusion in, hence
returning the membrane potential to its resting level.
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• In fact after the sodium channels have closed, some of the
voltage-gated potassium channels are still open, and in
nerve cells there is generally a small hyperpolarization of
the membrane.
• This potential beyond the resting level is known as after
hyperpolarization.
• Hyperpolarization makes the membrane potential more
negative (the cell interior becomes more negative).
• Beyond this phase cellular accumulation of sodium and loss
of potassium are prevented by the continuous action of
Na,K-ATPase pumps.
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• To explain more fully the factors that cause
both depolarization and repolarization, we
need to describe the special characteristics of
two other types of transport channels through
the nerve membrane: the voltage-gated
sodium and potassium channels.
 Activation of Voltage gated channels

• Activation of the Sodium Channel

• This is caused by the depolarization of the
membrane from its resting value of about
-90mV to about between -70-50mV.
• There is a conformational change in the
activation gate causing it to open.
• This is called the activated stage and there is an
increased influx of sodium ions into the cell.
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• Inactivation of the sodium Channel
• This occurs immediately after depolarization
and sodium ions can no longer enter the cell
• The cell begins approaching the repolarization
stage.
• This causes the potassium channels to rapidly
begin to open allowing the eflux of K+ ions out
of the cell.
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• Activation of the Potassium voltage-gated channels
• During the resting phase the sodium channels are
closed,
• When the membrane becomes depolarized ,the
voltage change causes a slow conformational
opening of the these channels,
• And as soon as sodium channels become inactivated
potassium channels open rapidly to allow the
outward movement of K+ ions.
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• This figure shows the voltage-gated sodium
channel in three separate states. This channel
has two gates—one near the outside of the
channel called the activation gate, and
another near the inside called the inactivation
gate.
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• The upper left of the figure depicts the state
of these two gates in the normal resting
membrane when the membrane potential is –
90 millivolts. In this state, the activation gate is
closed, which prevents any entry of sodium
ions to the interior of the fiber through these
sodium channels.
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• Activation of the Potassium voltage-gated channels
• During the resting phase the sodium channels are
closed,
• When the membrane becomes depolarized ,the
voltage change causes a slow conformational
opening of the these channels,
• And as soon as sodium channels become inactivated
potassium channels open rapidly to allow the
outward movement of K+ ions.
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• This figure shows the voltage-gated potassium
channel in two states: during the resting state
(left) and toward the end of the action
potential (right).
• During the resting state, the gate of the
potassium channel is closed, and potassium
ions are prevented from passing through this
channel to the exterior.
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• When the membrane potential rises from –90
millivolts toward zero, this voltage change
causes a conformational opening of the gate
and allows increased potassium diffusion
outward through the channel.
• However, because of the slight delay in
opening of the potassium channels, for the
most part
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• They open just at the same time that the
sodium channels are beginning to close
because of inactivation.
• Thus, the decrease in sodium entry to the cell
and the simultaneous increase in potassium
exit from the cell combine to speed the
repolarization process, leading to full recovery
of the resting membrane potential within
another few 10,000ths of a second.
REQUIREMENTS OF AN ACTION POTENTIAL

 Sodium channel
• As long as the membrane of the nerve fiber
remains undisturbed, no action potential occurs in the
normal nerve.
• A stimulus that disturbs the resting membrane
potential to a more positive value will rise voltage
itself and cause many voltage-gated sodium channels
to begin opening.
 Con’t….
• This allows rapid inflow of sodium ions, which
causes a further rise in the membrane
potential, thus opening still more voltage-
gated sodium channels and allowing more
streaming of sodium ions to the interior of the
fiber.
• This process continues until all the voltage-
gated sodium channels have become activated
(opened).
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• Then, within another fraction of a millisecond, the
rising membrane potential causes closure of the
sodium channels as well as opening of potassium
channels, and the action potential soon terminates.

 Threshold for Initiation of the Action Potential

An action potential will not occur until the initial rise in
membrane potential is great enough to create the cycle
of opening sodium channels.
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• The threshold for Initiation of the AP occurs
when the number of Na+ ions entering the fiber
becomes greater than the number of K+ ions
leaving the fiber.
• The threshold is the membrane potential at
which the action potential is inevitable. Inward
current depolarizes the membrane.
• If the inward current depolarizes the membrane
to threshold, it produces an action potential.
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• If the inward current is not sufficient to
depolarize the membrane to threshold, it does
not produce an action potential.
• Usually a rise in the RMP of about 15-30mV is
required.
• This is said to be the threshold for stimulation.
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• Inward current: is the flow of positive charge
into the cell. Inward current depolarizes the
membrane potential.
• Outward current: is the flow of positive charge
out of the cell. Outward current
hyperpolarizes the membrane potential
Con’t….
 Properties of Action potentials
 Direction of propagation:
• An action potential has no single direction of
propagation hence it will travel in both
directions away from the stimulus and along
all branches of the nerve fiber until the entire
membrane has become depolarized.
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 All-or-Nothing Principle
• Once an action potential has been elicited at
any point on the membrane of a normal fiber,
the depolarization process travels over the
entire membrane if conditions are right, or it
does not travel at all if conditions are not
right.
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 Refractory periods
• Once stimulated above threshold a cell becomes
refractory to further stimulation.

• This refractory include:

 Absolute refractory period:

• Is the period during which another action potential
cannot be elicited, no matter how large the stimulus
is.
• coincides with almost the entire duration of the
action potential.
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 the inactivation gates of the Na + channel are
closed when the membrane potential is
depolarized. They remain closed until
repolarization occurs.

 No action potential can occur until the

inactivation gates open.
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 Relative refractory period:
• begins at the end of the absolute refractory
period and continues until the membrane
potential returns to the resting level.
• An action potential can be elicited during this
period only if a larger than usual inward
current is provided, stronger than normal
stimuli are required to cause excitation.
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 The K+ conductance is higher than at rest, the
membrane potential is closer to the K.+
equilibrium potential and,
 Therefore, farther from threshold; more
inward current is required to bring the
membrane to threshold.
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Factors affecting the speed of propagation

• AP can travel along axons at speeds of between 0.1-

100m/s

• This means nerve impulses can get from one part of

the body to another in a few milliseconds and this
allows for fast response to stimuli.

• The factors affecting this speed include:

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• Temperature:
o The high the temperature the faster the speed
of propagation hence warm blooded animals
conduct impulses faster than cold blooded
animals.
• Axon diameter (fiber size):
o The larger the diameter the faster the speed
of conduction.
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o Increasing the diameter of a nerve fiber
results in decreased internal resistance; thus,
conduction velocity down the nerve is faster.
• Myelination:
o Myelin acts as an insulator around nerve
axons and increases conduction velocity.
o Myelinated nerve fibers conduct impulses
faster than unmyelinated ones.
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o This is partly due to the fact that the voltage
gated ion channels are found only at nodes of
Ranvier and between nodes are myelin sheaths
which are good electrical insulators.
o An AP can “jump” large distances from node to
node (1mm) hence increasing speed and this
process of conduction is called saltatory
conduction.
o Myelinated nerves exhibit saltatory conduction.
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