Action Potential of

The Excitable Tissues

(Nerves + Muscles)
Red: very important.
Green: Doctor’s notes.
Yellow: numbers.
Gray: notes and explanation.

Physiology Team 436 – Musculoskeletal Block Lectures 2 + 3

Lecture: If work is intended for initial studying.

Review: If work is intended for revision.
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 Objectives

o Discuss the resting membrane potential and its genesis.

o Know the ionic channels involved in resting membrane
potential.
o Describe the function Na+-K+ pump and the stages of action
potential.
o Explain the threshold Potential, local Response and action
Potentials.
o Describe the electrical changes in membrane potential during
the action potential, their chemical bases and excitability
changes.
o Describe conduction along nerve fibers, role of myelination
and how nerve fibers are classified.
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 Basic Physics of Membrane Potentials
Membrane potentials caused by ion concentration } The Nernst equation describes the relation of
} Differences across a selectively permeable diffusion potential to the ion concentration
membrane: across a membrane: we will later apply this in
resting membrane potential. The Nernst equation has a
The potassium concentration is great inside a nerve fiber physiological application when used to calculate the potential
membrane but very low outside the membrane. Because of of an ion of charge z across a membrane.
the large potassium concertation gradient from inside toward
outside, there is a tendency for extra numbers of potassium
ions to diffuse outward through the membrane. When they
do, they carry positive charge to the outside. Thus, creating
negativity inside because of negative anions (proteins,
EMF= electromotive force. Z= electrical charge of an ion
sulphate, phosphate ions, large molecules) cannot
leave the cell. that remained behind and DO NOT diffuse } The Goldman Equation is used to calculate the
outward with the potassium.
diffusion potential when the membrane is
(remember: diffusion from high concentration à low permeable to several ions
concentration.)

3 ONLY IN MALES’ SLIDES

 Resting Membrane Potential of Nerves (RMP):
Transport properties of the resting nerve membrane for sodium and
} RMP: it is the potential difference across potassium:
the cell membrane during rest, without • Sodium-Potassium pump (active transport)
stimulation between the inner side and the • K+ Leak Channels:
outer side, and it is relatively –ve inside.
} Measurement of RMP: using voltmeter

} Normal Values : -70 in medium sized

nerves and -90 mv in large nerve fibers.
(inside the fiber is 90 times more negative)
} During rest, the membrane is
polarized (the membrane is a wall
between the positive outside and negative
inside)
} There is high molecules of K+ inside the
cell and high molecules of Na+ outside the
cell. • Potential: difference in charge across plasma membrane.
• Current: flow of charge (ions) from one point to another.

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 Causes (Origin) of Resting Membrane Potential (RMP):
The important factors in the establishment of the normal resting
membrane potential of -90 millivolts. } 2- Contribution of Na diffusion through the
} 1- Contribution of K+ diffusion potential:- nerve membrane:
• The cell membrane has tendency to pump potassium (K) • Very small amount of Na+ diffuses into the cell (from outside
(positive charge) out, from high to low, (outflux), causing –ve to inside) down its concentration gradient.
charge inside, through K leak channels, down its • The membrane is only slightly permeable to Na+ through K-
concentration gradient. Na leak channels.
(producing energy like Niagara falls, from high to low which gives w

energy to Canada)
• Result: Electro-positivity outside and electro-negativity inside. } 3- Contribution of the Na+-K+ pump:
• RMP is 100 times more permeable to K+ than Na+. • This is a powerful electrogenic pump on the cell membrane.
(These K+ leak channels may also leak sodium ions slightly • maintains concentration gradients of K+ and Na+ between
but are far more permeable to potassium than sodium) the two sides of the membrane.
• K diffusion contributes far more to resting • It pumps 3 Na+ to outside & 2 K+ to inside, causing a net
membrane potential. (most important) ‫رﻛز ﻋﻠﯾﮭﺎ اﻟدﻛﺗور‬ loss of +Ve ions from inside, returning the nerve fibre to the
resting state (-4 mV).

5 Remember: Non-diffusible anions (proteins, sulphate, phosphate ions, large molecules) cannot leave the cell. Therefore, they also contribute to the negativity
Cont.: Origin of the Normal Resting Membrane
Potential
• Establishment of resting membrane potentials in nerve fibers • How did we get this value? Using the
under three conditions: Goldman equation:
1. When the membrane potential is caused entirely by K+ • E.M.F of K+ = -94 millivolts.
diffusion: EMF of K+= -94 mV • E.M.F of Na+ = +61 mV. (that’s why
2. When the membrane potential is caused by diffusion of the membrane is SLIGHTLY
both Na+ & K+ = -86 mV permeable to Na+)
3. When membrane potential is caused by diffusion of both • Using this value in the Goldman
Na+ & k+ AND Electrogenic Na+/K+ pump = -90 mV equation gives a potential inside the
membrane of −86 millivolts.

So the NET MEMBRANE POTENTIAL would be:-

• Diffusion potential (caused by K+ & Na+ diffusion) + Electrogenic Na+/K+
pump
• (-86 mV ) + (- 4mV) = -90 mV

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ONLY IN MALES’ SLIDES
 Action Potential (AP):
} Nerve signals are transmitted by action potentials, which are rapid
changes in the membrane potential that spread rapidly along the
nerve fiber membrane. Each action potential begins with a sudden
change from the normal resting negative membrane potential to
a positive potential and ends with an almost equally rapid
change back to the negative potential.
} Action Potential: a sudden reverse of membrane polarity (of
charges) produced by a stimulus to produce a physiological effect
such as:
o Transmission of impulse along nerve fibers (transmission of nerve
signals)
o Release of neurotransmitters
o Muscle contraction
o Activation or inhibition of glandular secretion
} Only Excitable tissue (Nerve and muscles) respond to action
potential.
} Firing = excitability = action potential = nerve impulse

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Stages of Action Potential (AP):
1- Resting stage / Initiation 2- Depolarization 3- Repolarization
of Action potential
• It is the resting membrane • The membrane suddenly becomes • K+ outflux through opening
potential before the action permeable to Na+ ions causing Na+ Voltage gated potassium channels,
potential begins. The influx to the interior of the axon this high K conductance (flow) to
membrane is “polarized”. (upstroke) through opening Voltage outside, causes the normal negative
gated sodium channels (positive resting membrane
• Initiation: The (polarized) feedback). potential.(Negative inside)
resting membrane potential • The membrane charges reverse (more • (Na+ channels begin to close and
rises from -90 to 0. (Gradual positive inside) the K+ channels open.)
depolarization) due to • Membrane potential rises from 0 to + 35 • This channel is slow, which leads to
threshold stimulus. mv, so all Na channels begin to close the next step.
suddenly. à (Depolarization ends)
• This channel ends fast.

A state of Hyperpolarization follows repolarization. *Will be explained later*

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 Excitation:
*The process of eliciting the action potential*
} Basically any factor that causes sodium ions to begin to diffuse inward
through the membrane in sufficient numbers can set off opening of
sodium channels. This opening of the sodium channels can result from
mechanical disturbance of the membrane, chemical effects on the
membrane, or passage of electricity through the membrane

Threshold for excitation and “Acute local potentials”

Threshold stimulus:
•The membrane potential at which occurrence of the action potential
is inevitable.
•When a stimulus is strong enough to move RMP from its resting
value (-90) to the range of -70mV to -55mV (-65 to 55) which leads
to production (start) of an AP or depolarization.
Subthreshold stimulus / Acute subthreshold potential:
•Stimulus that results in local depolarization. (local action potential)
(does not propagate or move along).
•When stimulus is below the threshold.
All or nothing principle: When threshold value for excitation is
reached, a full Action Potential is produced, so its intensity can not be
increased by increasing stimulus intensity
(suprathreshold).
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Types of Transport Channels Through the Nerve
Membrane
} There are two types:
The voltage gated Na+ channel has two gates:
1. Voltage gated Na+ channels
2. Voltage gated K+ channels.
} What opens the voltage gated channels? A stimulus Has 2 gates
strong enough to depolarize them to threshold.
Activation gate Inactivation gate

on the outer side of on the inner side of

membrane membrane

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 First: The Na+ Voltage-Gated Channel: Has three
states.
1.Resting state 2.Activated state 3.Inactivated state

oThe activation gate is Threshold Depolarizing Stimulus: moves

the MP from its resting value (-90 mV ) to its A few milliseconds after the activation
closed in the resting cell, gate opens, the channel becomes
when the MP* = RMP* is: threshold value (-65 to -55mV)
inactivated: At the peak of AP the
o-70 to -90 mV. This opens the activation gate. inactivation gate will close the inactivation
( NB in this case BOTH the activation gate & gate will NOT open by a second stimulus
üThis prevents entry of à & the cell becomes
Na+ to the interior of the inactivation gate are open ) à permeability to
Na+ becomes increased 500 to 5000 times à Refractory( ‫ )ﻣﻣﺎﻧﻌﺔ‬to another
cell through this gate stimulation
Na+ influx
*Na+ flows into the cell in large amounts* *This goes on until the MP has gone back
to its resting ( RMP) level ( -70 to -
90mV)*
*The activation gate is still open
the inactivation gate is closed*

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 Second: Potassium Voltage Gated Channel
(Repolarization)
• Has one gate only .
1. During the resting state:- the gate is closed and K+ can not go out to the
exterior
2. Shortly after depolarization (when the membrane potential rises from -90
mV towards zero):-
• The sodium channel begins to be inactivated
• The potassium channel opens
• K+ exits ( called K+ Efflux)* à Repolarization

#435 TEAM
‫ ﺳرﯾﻌﺔ اﻹﻏﻼق ﻓﺑﻣﺟرد ﺣدوث ﺗﻐﯾر ﻓﻲ اﻟﻔوﻟت ﺗﻔﺗﺢ اﻟﺑواﺑﺔ‬, ‫ ﺳرﯾﻌﺔ اﻟﻔﺗﺢ‬: ‫ﺑواﺑﺎت اﻟﺻودﯾوم‬
.‫وﯾدﺧل ﻓوج ﻣن اﻟﺻودﯾوم‬
sodium voltage-gated channel opens and closes in only milliseconds. And
if it reaches 35mV and doesn't close it may cause epilepsy ‫اﻟﺻرع‬

‫ ﺑطﯾﺋﺔ اﻹﻏﻼق‬, ‫ ﺑطﯾﺋﺔ اﻟﻔﺗﺢ‬: ‫ﺑواﺑﺎت اﻟﺑوﺗﺎﺳﯾوم‬

potassium voltage-gated channels open and close slowly and that's what
causes hyperpolarization

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‫‪Voltage gated Na+ channels‬‬ ‫‪video‬‬

‫اﻟدﻛﺗور ﻧﺑﮫ ﻋﻠﻰ اﻟرﺳﻣﺔ وﻗﺎل اﻧﮭﺎ‬

‫ﻣﮭﻣﺔ ﻣرة‬

‫‪13‬‬
 Action Potential (AP)
We need to start from the baseline (Resting State of the cell,
Reversal Potential = RMP)A threshold Stimulus will lead to:
+ 35 mV 1) Depolarization.
2) Repolarization phase.
3) In some neurons there is a 3rd phase called :Hyperpolarization

Threshold Potential
(Firing Level)
= -50 to -65 mV

RMP= -90 mV

Increasing Stimulation

* Action potential occurs when voltage-gated channels are opened!!

Q :What opens the voltage gated channels ?

( positive after-potential )
Opened by a stimulus strong enough to depolarize them to
threshold. video
14 ONLY IN FEMALES’ SLIDES
Further Explanation:

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Hyperpolarization:
} Hyperpolarization (Positive after-potential):
Hyperpolarization is a change in a cell's membrane potential
that makes it more negative inside and more positive outside,
more than resting membrane potential.)
} It inhibits action potentials by increasing the stimulus
required to move the membrane potential to the action
potential threshold.
} Towards the end of each action potential (following
Na-K Pump brings
repolarization) and continuing for a short period of time, the
MP back to its
membrane becomes more permeable to potassium resting value
ions. The increased outflow of potassium ions carries
positive charges. (the K+ conductance is higher than at
rest.)
} Na-K pump now starts to move Na+ out & K+ in against
their concentration gradient.
} While hyperpolarized, the neuron is in a refractory period.
Hyperpolarization

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What Happens After Action Potential? video
} Refractory period: few milliseconds
• Time during which can’t stimulate neuron a second time
• Happens until recovery of resting potential
} Two stages:
1. Absolute refractory period:
• The period during which a second action potential cannot be
elicited, even with a strong stimulus. (No new action potential
possible).
” ‫“ﯾﻌﻧﻲ ﻣﮭﻣﺎ ﻋطﯾﻧﺎ ﻣﺣﻔز ﺛﺎﻧﻲ ﻣﺎﯾﺳﺗﺟﯾب‬
2. Relative refractory period:
• Can trigger new action potential if stimulus is very strong.

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Summary of Action Potential : “EXTRA”

When membrane
potential (mV) reaches
- 70 Na gates will open ,
and the gates will close
when (mV) reaches
+ 30.

K gates will be open

when (mV) reaches
+30 , and close when it
reaches -90 .

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 The Neuron
} Definition: Unit of function of the central nervous
system.
1- Soma: cell body
2- Dendrites: carry nerve impulses
from surroundings to soma.
3- Axon hillock: start of action potential
(because it has a lot of voltage gated Na channels)
4- Axon and axon terminal.
Axon with myelin sheath Axon without myelin sheath
Only in male slides:
Myelinated axons diameter: >1um Unmyelinated axon diameter: • An Excitable tissue is the tissue
Schwann cells deposit <1um has the capability to respond to
sphingomyelin - Type C: in the Post ganglionic an adequate stimulus.
(which wraps around the axon) Autonomic fibers, and Pain fibers. • Examples are: nerves and
1- increases conduction velocity Also has schwann cells but not muscles
2- insulation by the membrane wrapped around the axon.
of Schwann cells. (‫) ﻋزل‬
19 ONLY IN FEMALES’ SLIDES
 Direction of AP Propagation (Conduction) video
} Artificial Electrical Stimulation :-

} Under Artificial condition of electrical

stimulation in the laboratory , the
AP propagates in both directions .

} But normally, AP starts in axon

hillock & propagates distally in one
direction Azaxon hillock
} AP starts at axon hillock Because it is full of
voltage gated Na channels

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Propagation of Action Potential

Myelinated nerve fibers Non- myelinated nerves

Saltatory conduction ( jumping) (local circuits)=point to point

o Many times faster transmission o Slower

o Action potential skips from one o Depolarization pass by local
node of Ranvier to the next
circuits.
Value:-
1- ↑ velocity of conduction of nerve
impulses
2- Conserve energy for axon because
only nodes depolarize
‫ أﻗل ﺑﺎﻟﺗﺎﻟﻲ ﯾﺣﺗﺎج طﺎﻗﺔ أﻗل ﻟذﻟك ﯾ ﻌﺗﺑر‬AP ‫ﻻن ﻋدد‬
energy conserving

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Propagation of Action Potential

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Conduction Velocity
} It is the speed at which action potentials are conducted (propagated)
along a nerve or muscle fiber.
} Mechanisms that increase conduction velocity along a nerve (influences
speed of action potential): Small diameter àslower large diameter àfaster
1. Axon / Nerve diameter: transduction transduction
} The larger the diameter, the faster the speed of transmission because
large fibers offers less resistance to local current flow so, more ions will
flow.
AP ‫ ﻗﻠت اﻟﻣﻘﺎوﻣﺔ ﻓﯾزﯾد‬diameter‫ﻛل ﻣﺎ زاد ال‬ }
(‫)ﻋﻼﻗﺔ ﻋﻛﺳﯾﺔ‬ }
2. Myelination:
} Myelin is an insulator that makes it more difficult for charges to flow
between intracellular and extracellular fluids.
} The layers of Schwann cell membrane contain the lipid substance
sphingomyelin (a lipid substance) which is excellent electrical
insulator that decreases ion flow through the membrane.
} Node of Ranvier: small uninsulated area where ions can flow with ease.

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 What Happens if Myelination is Lost? video
} Multiple sclerosis:
• Autoimmune disease (Immune system attacks
the myelin sheaths surrounding axons as well as
the axons themselves).
• Usually affect young adults.
• Causes blindness, problems controlling muscles
,ultimately paralysis.

Scar tissue (scleroses) Other now unmyelinated

The myelin sheaths are lost replaces some damaged cells axons sprout Na+ channels

24
Extra: “435” Excitation-the process of eliciting the action potential
(Threshold for excitation and “Acute Local Potentials”)

25
 ONLY IN FEMALES’ SLIDES

} Changes (a series of changes in polarity) that occur through the nerve

after stimulation by threshold stimulus:
} 1- Chemical changes.
} 2- Thermal changes.
} 3- Excitability changes.
} 4- Electrical changes (nerve action potential):
} It is the potential difference along the nerve membrane after stimulation by one
threshold stimulus.
} Most important factors:
o Threshold stimulus, and Voltage-gated Na and K channels.
o Nerve signals (impulses) which are transmitted via nerve action. They’re transmitted as a
wave of depolarization.
} - Oscilloscope: Measures rapid changes in membrane potential.

Propagation: action potential propagates through the nerve to stimulate other neurons
(starts from axon hillock because it has the most Voltage gated sodium channels)

26
Quiz

} https://www.onlineexambuilder.com/rmp-ap/exam-117621

Link to Editing File

(Please be sure to check this file frequently for any edits or updates on all of our lectures.)

References:
• Girls’ and boys’ slides.
• Guyton and Hall Textbook of Medical Physiology (Thirteenth Edition.)
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 Thank you!

.‫ اﻋﻣل و أﻧت ﺗﻌﻠم أن ﷲ ﻻ ﯾﺿﯾﻊ أﺟر ﻣن أﺣﺳن ﻋﻣﻼ‬،‫ اﻋﻣل ﻟﺗﻣﺳﺢ دﻣﻌﺔ‬،‫اﻋﻣل ﻟﺗرﺳم ﺑﺳﻣﺔ‬

The Physiology 436 Team:

Nouf Aloqaili Fahad Al Fayez Team Leaders:
Rana Barasain Muhammad Al Mutlaq Qaiss Almuhaideb
Norah Alshabib Lulwah Alshiha
Sundus Alhawamda
Ruba Barnawi Contact us:
Heba Alnasser
Lama Alfawzan Physiology436@gmail.com
@Physiology436

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