ACTION POTENTIAL:
Dr. Ayisha Qureshi
Assistant Professor
MBBS, MPhil
DEFINITIONS:
Stimulus:
A stimulus is an external force or event which when applied to
an excitable tissue produces a characteristic response.
Subthreshold stimulus:
A stimulus which is too weak to produce a response is called a
Subthreshold stimulus.
Threshold stimulus:
The minimum strength of stimulus that can produce excitation
is called a Threshold stimulus.
Suprathreshold stimulus:
Stimuli having strengths higher than threshold stimulus are
called Suprathreshold stimuli.
REMEMBER:
IMPORTANT:
• Sodium voltage-gated
channels: are fast channels &
have 2 gates:
- An outer Activation
gate(closed in resting state)
- An Inner Inactivation
gate(open in resting state)
• Potassium channels are slow
channels & have only ONE
gate.
• These channels are different
from Sodium & Potassium
leak channels.
• The Sodium-Potassium PUMP
is present separately.
Sodium & Potassium voltage-gated
channels:
ACTION POTENTIAL:
Action Potential:
Definition:
An Action Potential is a self-propagating wave of
electro-negativity that passes along the
surface of the axolemma of the nerve fibers.
• We know that the inside of the nerve membrane
is negative with respect to the outside
(RMP=—90 mv)
• When an effective stimulus(threshold or
suprathreshold) is applied, the electrical charge
on the membrane is reversed: at the active part
of the nerve fibre the outside becomes negative
as compared to the corresponding region in the
interior. This is called DEPOLARIZATION and forms
the Action Potential.
PHASES OF AN ACTION POTENTIAL:
Phase 1: Depolarization
Phase 2: Repolarization
Phase 3: Hyperpolarization
IONIC BASIS OF AN ACTION POTENTIAL:
1. DEPOLARIZATION: Sodium (Na) Influx
2. REPOLARIZATION: Potassium (K) Efflux
3. HYPERPOLARIZATION: Leakage of excess
Potassium (K) ions through the slow closing K
channels.
4. RETURN OF THE AP TO THE RMP FROM
HYPERPOLARIZATION: Sodium-Potassium
Pump
Why does the depolarization not reach the
Nernst potential of +66mv for sodium?
There are 2 main reasons. At +35 mv:
• Sodium Influx stops because Inactivation gates
of Sodium channels close although the
activation gates are open & thus no sodium
can enter
• Potassium Efflux starts because slow
Potassium channel gates open and potassium
moves out.
State of SODIUM channel gates:
• Resting state:
- Inactivation gates: OPEN
- Activation gates: CLOSED
• Depolarization:
- Activation gates: OPEN
- Inactivation gates: OPEN
• Peak:
- Inactivation gates: CLOSED
- Activation gates: OPEN
• Repolarization:
- Inactivation gates: OPEN
- Activation gates: CLOSED
VIVA QUESTIONS:
• AFTER-DEPOLARIZATION:
The descending limb of the action potential
does not reach the baseline abruptly, but it
shows a delay of several milliseconds. This is
due to decreased rate of K efflux at this time.
The excitability & conductivity of the fibre are
increased during this phase.
• AFTER-HYPERPOLARIZATION:
Same as Hyperpolarization....
DEFINITIONS:
LATENT PERIOD:
It is the time period between the application of a stimulus and the
start of the response (Action Potential)
DEPOLARIZATION:
When during the transit changes in the action potential, the Potential
difference between the inside of the membrane (-90mv) and
outside (0mv) decreases it is called depolarization. ( the tracing
will move upwards in the AP diagram)
REPOLARIZATION:
A return to the resting membrane potential from either direction (i.e.
de- or hyper-polarization) is called repolarization.
HYPERPOLARIZATION: When during the transit changes in the action
potential, the Potential difference between the inside of the
membrane (-90mv) and the outside (0mv) increases it is called
Hyperpolarization.
PROPAGATION OF AN ACTION
POTENTIAL:
Conduction of an Action
Potential in an Unmyelinated
nerve fibre:
Question:
• Why and how does the action potential
spread in the forward direction only?
• Why does NOT the action potential spread in
the reverse direction?
Unmyelinated Nerve fiber
• Once an action potential is initiated at the axon hillock, no further
triggering event is necessary to activate the remainder of the nerve
fiber. The impulse is automatically conducted throughout the
neuron.
• For the action potential to spread from the active to the inactive
areas, the inactive areas must somehow be depolarized to
threshold. This depolarization is accomplished by local current flow
between the area already undergoing an action potential and the
adjacent inactive area
• This depolarizing effect quickly brings the involved inactive area to
threshold, at which time the voltage-gated Na channels in this
region of the membrane are all thrown open, leading to an action
potential in this previously inactive area. Meanwhile, the original
active area returns to resting potential as a result of K efflux.
VIVA Question:
• Does the action potential become weak (decremental)
as it travels down the nerve fiber?
• NO, the action potential does NOT become weak as it
travels down the nerve fiber. In fact, the AP does NOT
travel down the nerve fiber but triggers a new AP in
every new part of the membrane. It is like a “wave” at
a stadium. Each section of spectators stands up (the
rising phase of an action potential), then sits down (the
falling phase) in sequence one after another as the
wave moves around the stadium. The wave, not
individual spectators, travels around the stadium.
Thus, the last action potential at the end of the
axon is identical to the original one, no matter
how long the axon is. In this way, action
potentials can serve as long-distance signals
without becoming weak or distorted or
decremental.
VIVA Question:
• Why does NOT the action potential spread in the
reverse direction?
• If AP were to spread in both directions, which is
forward and backward, it would be chaos, with
the numerous AP’s bouncing back & forth along
the axon until the axon eventually fatigued. This
does not happen due to the Refractory period.
During and after the generation of an AP, the
changing status of the voltage-gated Na and K
channels prevents the AP from being generated
in these areas again.
CONDUCTION OF AP IN A
MYELINATED NERVE FIBER:
Continuous Conduction
• Occurs in unmyelinated axons.
• In this situation, the wave of de- and repolarization simply
travels from one patch of membrane to the next adjacent
patch.
• APs moved
in this
fashion
along the
sarcolemma
of a muscle
fiber as well.
• Analogous to
dominoes
falling.
In a Myelinated Nerve Fibre an Action Potential
travels by SALTATORY Conduction, which is in
a jumping manner from one Node of Ranvier
to the next Node of Ranvier, While in an
Unmyelinated Nerve Fibre an Action Potential
travels from POINT TO POINT.
At the nodes of ranvier, there are an increased
number of Sodium channels present.
• Which do you think has a faster rate
of AP conduction – myelinated or
unmyelinated axons?
• The answer is a myelinated axon.
• If you can’t see why, then answer this
question:
Could you move 100ft faster if you walked
heel to toe or if you bounded in a way that
there were 3ft in between your feet with each
step?
• Which do you think would conduct
an AP faster – an axon with a large
diameter or an axon with a small
diameter?
• The answer is an axon with a large diameter.
• If you can’t see why, then answer this
question:
Could you move faster if you walked through a
hallway that was 6ft wide or if you walked
through a hallway that was 1ft wide?
Name the events & ions responsible for:
– Depolarization
– Repolarization
– Hyperpolarization OR Undershoot
– Return of the AP from the Overshoot to
the RMP
PROPERTIES OF A NERVE FIBRE:
1. ALL OR NONE LAW
(also called the All or Nothing Law)
On application of a stimulus, an excitable membrane
either responds with a maximal or full-fledged action
potential that spreads along the nerve fiber, or it does not
respond with an action potential at all. This property is
called the all-or-none law.
(This is in direction proportion to the strength of the stimulus applied.)
e.g: This is similar to firing a gun. Either the trigger is NOT
pulled sufficiently to fire the gun (subthreshold stimulus)
OR it is pulled hard enough to fire the gun (threshold is
reached). Squeezing the trigger harder does not produce
a greater explosion, just as pulling the trigger halfway
does not cause the gun to fire halfway.
Some Action Potential Questions
• What does it mean when we say an AP is “all
or none?”
– Can you ever have ½ an AP?
• How does the concept of threshold relate to
the “all or none” notion?
• Will one AP ever be bigger than another?
– Why or why not?
2. Refractory period:
- ABSOLUTE REFRACTORY PERIOD
- RELATIVE REFRACTORY PERIOD
2a: ABSOLUTE REFRACTORY PERIOD
Definition:
Once an action potential has been generated , the time period during which even a
suprathreshold stimulus will fail to produce a new action potential is called the
Absolute Refractory period.
During this time the membrane becomes completely refractory (‘stubborn’ or
‘unresponsive’) to any further stimulation.
It corresponds to the entire Depolarization phase & most of the Repolarization phase.
Due to Absolute refractory period, one AP must be over before another can be
initiated at the same site. APs cannot be overlapped or added one on top of
another.
• BASIS OF AN ABSOLUTE REFRACTORY PERIOD:
During the depolarization phase of AP, the voltagegated Sodium channels have still NOT reset to
their original position. For the Sodium channels
to respond to a stimulus, 2 events are important:
1. Sodium channels be reset to their closed but
capable of opening position. i.e: inactivation
gates open and activation gates closed.
2. The Resting membrane potential must be reestablished.
2b: Relative Refractory Period
Definition:
Following the absolute refractory period is seen a
period of short duration during which a second
action potential can be produced, only if the
triggering event is a suprathreshold stimulus.
This period is called the Relative Refractory
Period.
It corresponds to the last half of the Repolarization
phase.
• Basis of a Relative Refractory Period:
An action potential can be produced by a
suprathreshold stimulus because of the following
reasons:
1. By the end of the repolarization phase, some Na
channels have reset while some K channels are
also still open.
2. Thus, a greater than normal triggering event
(suprathreshold stimulus) is required to produce
an AP.
Absolute VS Relative Refractory
Period
• Imagine, if you will, a toilet.
•
When you pull the handle, water floods the
bowl. This event takes a couple of seconds and you
cannot stop it in the middle. Once the bowl empties,
the flush is complete. Now the upper tank is empty.
If you try pulling the handle at this point, nothing
happens (absolute refractory). Wait for the upper
tank to begin refilling. You can now flush again, but
the intensity of the flushes increases as the upper
tank refills (relative refractory)
In this figure, what do the red
and blue box represent?
VM
TIME
What is the significance of the REFRACTORY
PERIOD (both absolute & relative):
1. There is no fusion or summation of the action potentials. This intermittent, ie. Not
continuous conduction of nerve impulses is one of the reasons why a nerve fibre
can respond to continuous stimulation for hours without getting tired. Thus, it
decreases fatigue in a nerve fibre.
2. The Action Potentials are produced separate from each other. So, a new AP is
produced in each part of the nerve fibre. This ensures that the AP does not die out
as it is conducted along the membrane.
3. Only a certain number of Action Potentials can be produced in a nerve fibre
because the interval between any 2 action potentials cannot be shorter than the
Absolute Refractory Period. This prevents fatigue of the nerve fibers and sets an
upper limit on the maximum numbers of AP that can be produced in a nerve fibre
in a given period of time.
4. By the time the original site has recovered from its refractory period and is
capable of being restimulated by normal current flow, the action potential has
been propagated in the forward direction only and is so far away that it can no
longer influence the original site. Thus, the refractory period ensures the one-way
propagation of the action potential down the axon away from the initial site of
activation.
3. COMPOUND ACTION POTENTIAL:
3. Compound Action Potential is seen
in a “nerve trunk” & NOT a nerve fibre:
• An action potential having
more than one peak/spike is
called a Compound action
potential.
CAUSE: A nerve trunk contains
many nerve fibres differing
widely in their excitability &
different speeds of conduction
of AP. Multiple peaks are
recorded with the AP from
fastest conducting nerve fibre
first to be recorded followed
by the slower ones....
4. STRENGTH-DURATION CURVE:
4. Strength Duration Curve:
Strength duration curve represents 2 (two) factors which
control the final strength of the stimulus. These are:
i. Voltage or current strength of the stimulus applied
ii. Duration of the stimulus
By varying the above 2 factors and plotting the results, a curve
is obtained which is called the STRENGTH-DURATION
CURVE. (See Mushtaq, vol. 1, ed. 5th , page: 118-119)
It is obvious that a stimulus with a low voltage will have to be
applied for a long period of time to reach the threshold
level, while high voltage stimulus will need a much
shorter duration....
4. Strength Duration Curve:
• RHEOBASE:
It is the minimum voltage stimulus which when applied
for an adequately prolonged time will produce an AP.
• UTILIZATION TIME:
The minimum time that a current equal to rheobase must
act to induce an AP is called the Utilization Time.
• CHRONAXIE:
It is the minimum duration for which a stimulus equal to
twice the rheobase value has to be applied in order to
start an AP.
Tissues which are more excitable will have a shorter chronaxie and vice
versa...
PROPERTIES OF AN ACTION POTENTIAL:
1.
2.
3.
4.
5.
All or none Law
Absolute & Relative Refractory period
Compound Action Potential
Strength-Duration Curve
Conduction through
- A myelinated nerve fiber (Saltatory
conduction)
- An unmyelinated nerve fiber (Point to
Point Conduction)