ACTION POTENTIAL:

Dr. Ayisha QureshiAssistant 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: DepolarizationPhase 2: Repolarization

Phase 3: Hyperpolarization

IONIC BASIS OF AN ACTION POTENTIAL:

1. DEPOLARIZATION: Sodium (Na) Influx2. REPOLARIZATION: Potassium (K) Efflux3. 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?

- ABSOLUTE REFRACTORY PERIOD- RELATIVE REFRACTORY PERIOD

2. 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 voltage-

gated 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 re-established.

2b: Relative Refractory PeriodDefinition: 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)

TIME

VM

In this figure, what do the red and blue box represent?

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 appliedii. 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. All or none Law2. Absolute & Relative Refractory period3. Compound Action Potential4. Strength-Duration Curve5. Conduction through

- A myelinated nerve fiber (Saltatory conduction)

- An unmyelinated nerve fiber (Point to Point Conduction)