ACTION POTENTIAL OF ACTION POTENTIAL OF NERVE FIBER / SKELETAL NERVE FIBER / SKELETAL

MUSCLE:MUSCLE: An abrupt pulse like change in membrane An abrupt pulse like change in membrane

potential, lasting for fraction of a second. potential, lasting for fraction of a second.

During action potential there is reversal of During action potential there is reversal of potential. (inside +, outside potential. (inside +, outside --).).

Nerve impulse is being conducted along a nerve Nerve impulse is being conducted along a nerve fiber = action potential is being conducted.fiber = action potential is being conducted.

DepolarizationDepolarization= loss of negativity inside.= loss of negativity inside.

RepolarizationRepolarization= return of negativity inside.= return of negativity inside.

THE NERVE IMPULSE (ACTION POTENTIAL) Is a self propagating wave of electro negativity that passes along the surface of axolemma of nerve fibers.

It is the progression of ionic changes

It is the potential difference that travels

3

RESTING STATE:

 a)  all voltage-gated and chemically-gated ion channels are closed 

b)  membrane potential approximately -90 mV 

c)  the Na+ K+ ATPase pumps are operating (3 Na+ out/2 K+ in per ATP hydrolysis)

THE STIMULUS

Is an external force or event which when applied to an excitable tissue produces a characteristic response.

Electrical

Hormonal/ chemical

Thermal

Mechanical

Electromagnetic

Osmotic

THRESHOLD

The minimum strength of stimulus that can produce excitation is called threshold. 15-30 mv

Latent Period:

The time elapsed between application of the stimulus and start of action potential. 0.1-0.2 msec

DEPOLARIZATION PHASE:  a)  a stimulus of threshold strength or greater causes the gated Na+ ion channels to open; Na+ ions diffuse into the cytoplasm

b)  membrane potential reverses from approximately -70 mV to approximately +30 mV

c)  the Na+ K+ ATPase pumps are operating (3 Na+ out/2 K+ in per ATP hydrolysis)

REPOLARIZATION PHASE: a)  the gated Na+ ion channels slowly close; Na+ ions can no longer diffuse into the cytoplasm 

b)  meanwhile, the gated K+ ion channels open; K+ ions diffuse out of the cytoplasm

c)  membrane potential reverses again, dropping from approximately +30 mV to approximately -70 mV

d)  the Na+ K+ ATPase pumps are operating (3 Na+ out/2 K+ in per ATP hydrolysis)

HYPERPOLARIZATION PHASE:a)  the gated Na+ ion channels have closed; Na+ ions can no longer diffuse into the cytoplasm 

b)  meanwhile, the gated K+ ion channels slowly close; K+ ions can no longer diffuse out of the cytoplasm 

c)  membrane potential becomes more negative than the resting state, dropping to approximately -80 mV

d)  the Na+ K+ ATPase pumps are operating (3 Na+ out/2 K+ in per ATP hydrolysis) and will restore the resting state conditions

RMP -90 mV

Threshold -65 mV

0 mV

+35 to 40 mV

After Hyper-polarization (Undershoot) / Sub-normal period ( -95 mV )

[K+efflux continues, K+channels remain open for some time after RMP is reached].Here tissue is difficult to be excited.

Depolarization Repolarization[K+efflux]

Time (ms)

(Overshoot)

Peak

Membrane Voltage

(mV)

RMP -90 mV

[Rapid

Na+influx]

Completeopening of fast Na+ channels

Slow Repolarization/ K+accumulateExcitable/ Super-normal period

AfterDepolarization

(70% of repolarization / start of After-Depolarization)

Spike potential

(First 1/ 3 of repolarization)

Relative Refractory period

Absolute Refractory period [Na+ inactivation gates are still closed]

-65mV

Properties of action potentialProperties of action potential:: Sudden / abrupt in onsetSudden / abrupt in onset. Shows Spike potential.. Shows Spike potential. Of Of limited magnitude / amplitudelimited magnitude / amplitude(+35 to 40 mV)(+35 to 40 mV) Positive as well as negative course (Positive as well as negative course (biphasicbiphasic)) Short durationShort duration (may be few millisec).(may be few millisec). It obeys all or none lawIt obeys all or none law(if a stimulus is threshold or (if a stimulus is threshold or

suprathreshold suprathreshold action potential is produced with action potential is produced with its maximum amplitude, if subthreshold stimulus its maximum amplitude, if subthreshold stimulus not produced at all).not produced at all).

Self propagatingSelf propagating(automatically propagated in both (automatically propagated in both directions).directions).

Has a refractory periodHas a refractory period. (when there will be no . (when there will be no response to 2response to 2ndnd potential).potential).

Voltage gated channels:Voltage gated channels: At rest (At rest (--90mV) sodium activation gates on outside 90mV) sodium activation gates on outside

of membrane remain closedof membrane remain closed

For fraction of m sec in presence of threshold For fraction of m sec in presence of threshold stimulus, rapid sodium influx takes place stimulus, rapid sodium influx takes place depolarization (depolarization (--90mV to +35mV)90mV to +35mV)

There is delayed closure of inactivation gate on the There is delayed closure of inactivation gate on the inside.inside.

Repolarization due to activation of potassium Repolarization due to activation of potassium channels, +ions move out channels, +ions move out regain of negativity regain of negativity inside (repolarization)inside (repolarization)

Voltage gated channels:Voltage gated channels: At rest potassium gates situated on inside At rest potassium gates situated on inside

are closed (are closed (--90mV)90mV)

There is slow activation of potassium gates There is slow activation of potassium gates between +35mV to between +35mV to --90mV. Rapid 90mV. Rapid potassium efflux occurs.potassium efflux occurs.

Potassium channels are slow to open & Potassium channels are slow to open & slow to close. They will open when sodium slow to close. They will open when sodium gates are closed.gates are closed.

Remains closed at rest

Rapid sodium influx for fraction of millisec due to threshold stimulus

Delayed closure of inactivation gate at the end of depolarization

Potassium gates closed at rest.Repolarization due to activation of K channels, + ions move out repolarization. Only 1 gate for K on inside

K efflux. Threshold stimulus simultaneouslyto Na channels, a slow change in K channels.K channels will open when Na gates are closed.

Upstrokeis due to activation of sodium channelsrapid sodium influx inside becomes positive depolarization.

* threshold / firing / critical value: - 65 mV for sodium channels. It causes change in activation gate of sodium channels at -65 mV, complete opening of fast sodium channels.

Inactivation gates do not reopen till membrane Inactivation gates do not reopen till membrane becomes near to resting value, ibecomes near to resting value, i--e., the refractory e., the refractory period.period.

K+ becomes accumulated on outer sideK+ becomes accumulated on outer sideof of membrane in efflux, which slows down further membrane in efflux, which slows down further efflux efflux after 70% of repolarizationafter 70% of repolarization slow slow repolarizationrepolarization called called after depolarizationafter depolarization..

When potential has reached the resting value, it does When potential has reached the resting value, it does not stay there & becomes more negative & called not stay there & becomes more negative & called After hyperpolarization. After hyperpolarization.

It is because It is because when potential has reached resting when potential has reached resting valuevalue, some K channels are still open & , some K channels are still open & K efflux K efflux continuescontinues membrane becomes more negative.membrane becomes more negative.

Part of action potential between threshold value & Part of action potential between threshold value & beginning of after depolarization is called beginning of after depolarization is called SPIKE SPIKE POTENTIAL.POTENTIAL.

Recharging of nerve fibers requires action of Na-K ATPase pump.

Active process

Requires energy

Compound action potential: Multi-peaked action potential recorded from a

nerve trunk. For example: Sciatic nerve has number of nerve

fibers of different diameters & different velocity of conduction.

When action potential from different nerve fibers are recorded multiple peaks.

3 main peaks: A, B, C. A is further divided into alpha, beta, gamma,

delta. A & B types are myelinated & C type is

unmyelinated. Compound action potential is basis of

physiological classification of nerve fibers.A alpha fibers with maximum diameter have

Compound action potential:

Propagation of action Propagation of action potential in potential in unun--myelinatedmyelinatednerve fibers:nerve fibers:

Point to point conduction.Point to point conduction.

Local circuit of current is formed between Local circuit of current is formed between depolarized point & adjacent polarized point.depolarized point & adjacent polarized point.

Copyright © 2006 by Elsevier, Inc.

Propagation:

Rest

Opening of Na+ channels generates local current circuit that depolarizes adjacent membrane, opening more Na+ channels…

Stimulated(local depolarization)

Propagation(current spread)

OrthodromicOrthodromic & & AntidromicAntidromic Conduction:Conduction: An An axon can conduct in either directionaxon can conduct in either direction.. ORTHODROMICORTHODROMIC: Conduction of impulse : Conduction of impulse

from synaptic junctions or receptors along from synaptic junctions or receptors along axons to there termination.axons to there termination.

ANTIDROMICANTIDROMIC: Conduction in the opposite : Conduction in the opposite direction.direction.

SynapsesSynapses are unlike axons: are unlike axons: Conduction in 1 Conduction in 1 direction onlydirection only, so an antidromic impulse will , so an antidromic impulse will fail to pass the 1fail to pass the 1stst synapse they encounter & synapse they encounter & die out at that point.die out at that point.

StrengthStrength--duration curve:duration curve:

2mV2mV

1mV1mV

00 1 ms1 ms 2 ms2 ms

DurationDuration

strengthstrengthRheobaseRheobase

ChronaxieChronaxie

Utilization timeUtilization time

Nerve fiber has many properties:• Excitability• Conductivity• Refractory period• All or none lawThe units of excitability are:Rheobase & Chronaxie

Rheobase: It is the voltage/strength of stimulus, required just to excite the tissue ,e.g, 1mV.

Utilization time: The time for which Rheobase must be applied, to excitethe tissue is utilization time ,e.g, 2 ms.

Chronaxie: A time for which a stimulus double the rheobase (,i-e, 2mV) when applied, just excites the tissue ,e.g, 1 ms.

Clinical Application of Clinical Application of Chronaxie:Chronaxie:

Chronaxie has a particular value for a particular Chronaxie has a particular value for a particular tissue ,tissue ,

e.g, type A nerve fiber has minimum value of e.g, type A nerve fiber has minimum value of chronaxie that is they require less duration of chronaxie that is they require less duration of time to produce a response when a stimulus time to produce a response when a stimulus double the strength of rheobase arrives. double the strength of rheobase arrives.

Type A nerve fibers are more excitable as Type A nerve fibers are more excitable as compared to cardiac muscle.compared to cardiac muscle.

Clinical Application of Clinical Application of Chronaxie: (continued)Chronaxie: (continued)

In nerve injury In nerve injury repair procedurerepair procedure we we access the recovery, by finding access the recovery, by finding chronaxie of the effected nerve & chronaxie of the effected nerve & muscle.muscle.

Chronaxie shortens with recoveryChronaxie shortens with recovery

* Degree of damage to nerve fiber is * Degree of damage to nerve fiber is determined by measuring chronaxie.determined by measuring chronaxie.

BIPHASIC POTENTIAL:

EPSP Vs ACTION POTENTIAL: EPSP Vs ACTION POTENTIAL: Table 2Table 2--4 4 MushtaqMushtaq

Na+ first, then K+Na+ first, then K+To Na+ & K+ at one To Na+ & K+ at one time but Na+ influx is time but Na+ influx is much much greategreatethan K+ than K+ effluxefflux

Increased permeability to Increased permeability to ionsions

Absent; size is always the Absent; size is always the samesame

Present Present Decrement (decline of Decrement (decline of size with distance)size with distance)

obeyedobeyedNot obeyed; size directly Not obeyed; size directly proportional to intensity proportional to intensity of stimulusof stimulus

All or none lawAll or none law

presentpresentabsentabsentRefractory periodRefractory period

Self propagatingSelf propagating

2 2 msecmsecNil; remains localized, 20 Nil; remains localized, 20 msecmsec

Propagation & DurationPropagation & Duration

HighHighLowLowMagnitudeMagnitude

Action PotentialAction PotentialEPSPEPSPPropertyProperty

Refractory period:Refractory period: AbsoluteAbsolute: During depolarization & first 1/3 of : During depolarization & first 1/3 of

repolarization. Here sodium inactivation gates are still repolarization. Here sodium inactivation gates are still closed & will not open till potential reaches resting closed & will not open till potential reaches resting value.value.

RelativeRelative: From end of first 1/ 3 of repolarization to the : From end of first 1/ 3 of repolarization to the beginning of after depolarization (here stronger beginning of after depolarization (here stronger stimulus can produce action potential).stimulus can produce action potential).

Super normal periodSuper normal period: During After depolarization, : During After depolarization, there is super normal period. Tissue is most excitable. there is super normal period. Tissue is most excitable. Here potential is Here potential is –– 65 mV, so small change is required 65 mV, so small change is required to stimulate.to stimulate.

SubSub--normal periodnormal period: During After hyper: During After hyper--polarization it polarization it occurs, because tissue is difficult to be excited because occurs, because tissue is difficult to be excited because potential becomes potential becomes –– 95 mV.95 mV.

REFRACTORY PERIOD

ROLE OF CALCIUM IONS

Act as stabilizers of sodium channels

Alter the electrical state of sodium channels

Responsible for slow action potential in smooth and cardiac muscle cells

WALLERIAN DEGENERATION Changes in distal stump of injured nerve: (2 marks)

 

Axon & myelin sheath completely degenerate (secondary / Wallerian degeneration).

Simultaneous degeneration throughout length of nerve fiber.

Changes appear in 24 hrs & complete in 3 wks.

Continued conduction for 3 days post injury.

After 5th day all function is stopped.

 

HISTOLOGICAL CHANGES IN DEGENERATION OF NERVE:

 

Axoplasm breaks up into short segments.

Swelling of neurofibrils become tortuous & disappear after sometime.

Within few days, space containing axoplasm shows only a little debris.

Myelin sheath disintegrates fat droplets appear (8th to 32nd day).

Lecithin molecules present in myelin sheath completely hydrolyzed to glycerol, fatty acids, phosphoric acid & choline removed by increased number of macrophages (appearing as foam cells due to their high lipid content) or by blood stream.

Endoneurium remains intact within endoneurial tubes.

Schwann cells proliferate & their increased number along with fibrous tissue false neuroma. (True neuroma in regeneration)