Physiology Lec 14

PHYSIOLOGY 1
RESOURCE PERSON : DR TAYYABA

SATTAR
REFERENCE TEXT :
TEXTBOOK OF MEDICAL
PHYSIOLOGY
GUYTON & HALL
Membrane Potentials
and Action
Potentials
Relation of the Diffusion Potential to the Concentration
Difference
 Membrane Potentials caused by Diffusion
 “Diffusion Potential” caused by an ion concentration difference on

the
two sides of the membrane.
 The Nernst Potential:

The diffusion potential level across a membrane that exactly opposes
the net diffusion of a particular ion through the membrane is called
the Nernst potential for that ion
Goldman equation
• The Goldman-Hodgkin-Katz Equation:
Calculation of the Diffusion Potential when the Membrane Is Permeable to

Several Different Ions
• When a membrane is permeable to several different ions, the diffusion

potential
that develops depends on three factors:
(1) the polarity of the electrical charge of each ion
(2) the permeability of the membrane (P) to each ion
(3) the concentrations (C) of the respective ions on the inside (i) and outside (o)
of the membrane.
• Thus, gives the calculated membrane potential on the inside of the membrane
when two univalent positive ions, sodium (Na+) and potassium (K+), and one
univalent negative ion, chloride (Cl–), are involved.
Measuring the Membrane Potential
 The method for measuring the membrane potential is simple in
theory but often difficult in practice because of the small size of most
of the fibers.
 A small pipette filled with an electrolyte solution. The pipette is
impaled through the cell membrane to the interior of the fiber.
 Then another electrode, called the “indifferent electrode,” is placed in the

extracellular fluid,
 And the potential difference between the inside and outside of the
fiber is measured using an appropriate voltmeter.
 This voltmeter is a highly sophisticated electronic apparatus that is

capable of measuring very small voltages despite extremely high resistance to
electrical
fl ow through the tip of the micropipette, which has a lumen diameter usually
less than 1 micrometer and a resistance more than a million ohms.
 For recording rapid changes in the membrane potential during transmission of

nerve impulses, the microelectrode is connected to an oscilloscope
Origin of the Normal Resting Membrane
Potential
The normal resting membrane potential of –90 millivolts
1) contribution of the Potassium Diffusion Potential
2)Contribution of Sodium Diffusion Through the Nerve
Membrane.
3) Contribution of the Na+-K+ Pump.
1) contribution of the Potassium Diffusion
Potential
• Because of the high ratio of potassium ions inside to outside, 35:1
• Nernst potential corresponding to this ratio is –94 millivolts

2) Contribution of Sodium Diffusion Through the Nerve
Membrane
• the addition of slight permeability of the nerve membrane to sodium
ions, caused by the minute diffusion of sodium ions through the K+-
Na+ leak channels.
• The ratio of sodium ions from inside to outside the membrane is 0.1,
And Nernst potential for the inside of the membrane of +61 millivolts.
3) Contribution of the Na+-K+ Pump.
 Na+-K+ pump provides an additional contribution to the
resting potential.
 continuous pumping of three sodium ions to the outside for each
two potassium ions pumped to the inside of the membrane.
 The fact that more sodium ions are being pumped to the outside than
potassium to the inside causes continual loss of positive charges from
inside the membrane; this creates an additional degree of negativity
(about –4 millivolts additional) on the inside beyond that which
can be accounted for by diffusion alone.
Therefore, the net membrane potential with all these factors operative
at the same time is about –90 millivolts.
• In summary, the diffusion potentials alone caused
by potassium and sodium diffusion would give a
membrane potential of about –86 millivolts,
almost all of this being determined by potassium
diffusion.
• Then, an additional –4 millivolts is contributed to

the membrane potential by the continuously acting
electrogenic Na+-K+ pump, giving a net
membrane potential of –90 millivolts
Resting Stage of nerve
 –90 millivolts is the resting membrane potential (negative membrane
potential)
 Polarized membrane
 before the action potential begins.
 High resting conductance to K+
 Low conductance to Na+
Nerve Action Potential
• Property of excitable cell
• Rapid depolarization followed by repolatization
• Begins with a sudden change from the normal
resting negative membrane potential to a positive
potential
• Ends with an almost equally rapid change back to
the negative potential.
Depolarization Stage
At this stage sudden increases in the permeability of
sodium ions more positively charged sodium ions
to diffuse to the interior of the axon. immediately
neutralize the AP of resting membrane
positive AP depolarization.
Inward current of positive charge
Repolarization Stage
Within a few 10,000ths of a second after
high sodium ions permeability
the sodium channels begin to close
 the potassium channels open more than
normal.
Outward current of positive charge
Then, rapid diffusion of potassium ions to the
exterior re-establishes the normal negative resting
membrane potential. This is called repolarization of
the membrane.
Additional transport channels in action potential
A voltage-gated sodium channel is important in
both depolarization and repolarization of the nerve
membrane during the action potential
A voltage-gated potassium channel is important

role in increasing the rapidity of repolarization
of the membrane.
These two voltage-gated channels are in addition to the
Na+-K+ pump and the K+-Na+ leak channels that are
important in AP
Voltage-Gated Sodium Channel
This channel has two gates:
 The activation gate: Outside
 The inactivation gate: Inside
In the resting membrane: the activation gate is

closed, which prevents any entry of sodium ions to
the interior of the fiber through these sodium
channels
 Activation of the Sodium Channel Gate:
 When the membrane rising from –90 millivolts toward zero
 between –70 and –50 millivolts that causes a sudden

conformational change in the activation gate, flipping it all the way
to the open position.
 sodium ions can pour inward through the channel, increasing the
sodium permeability of the membrane as much as 500- to
5000- fold.
 Inactivation of the Sodium Channel
 The same increase in voltage that opens the activation gate
also closes the inactivation gate.
 The inactivation gate, however, closes a few 10,000ths of a second

after
the activation gate opens.
 That is, the conformational change that fl ips the inactivation gate to
the closed state is a slower process than the conformational
change that opens the activation gate.
 Therefore, after the sodium channel has remained open for a few
10,000ths of a second, the inactivation gate closes, and sodium
ions no longer can pour to the inside of the membrane.
 At this point, the membrane potential begins to recover back
toward the resting membrane state, which is the repolarization
process.
 Another important characteristic of the sodium channel

inactivation process is that the inactivation gate will not reopen
until the membrane potential returns to or near the original
resting membrane potential level.
 Therefore, it usually is not possible for the sodium channels to open

again without the nerve fiber’s first repolarizing.
Voltage-Gated Potassium Channel
The voltage-gated potassium channel in two states:
 During the resting state
 Toward the end of the action potential.
• In resting state : the potassium channel is closed, & potassium ions

are prevented from passing through this channel to the exterior.
 When the membrane potential rises from –90 millivolts toward zero,
this voltage change causes conformational opening of the gate
and allows increased potassium diffusion outward through the
channel.
Because of the slight delay in opening of the potassium
channels, 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.
Roles of Other Ions During the Action Potential
two other types of ions must be considered:

1. negative anions (of protein molecules, organic phosphate,& sulfate
compounds)
2. calcium ions.
1. Impermeant anions inside the nerve axon.

 ions cannot leave the interior of the axon
 responsible for the negative charge inside the fiber
2. Calcium Ions:
1) Calcium pump:
similar to the sodium pump
 pumps calcium ions from the interior to the exterior of the cell
membrane
 creating a calcium ion gradient of about 10,000-fold.

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PHYSIOLOGY 1

RESOURCE PERSON : DR TAYYABA

 Membrane Potentials caused by Diffusion

 “Diffusion Potential” caused by an ion concentration difference on

 The Nernst Potential:

Calculation of the Diffusion Potential when the Membrane Is Permeable to

• When a membrane is permeable to several different ions, the diffusion

 Then another electrode, called the “indifferent electrode,” is placed in the

 This voltmeter is a highly sophisticated electronic apparatus that is

 For recording rapid changes in the membrane potential during transmission of

• Because of the high ratio of potassium ions inside to outside, 35:1

• Nernst potential corresponding to this ratio is –94 millivolts

• Then, an additional –4 millivolts is contributed to

A voltage-gated potassium channel is important

In the resting membrane: the activation gate is

 When the membrane rising from –90 millivolts toward zero

 between –70 and –50 millivolts that causes a sudden

 The inactivation gate, however, closes a few 10,000ths of a second

 Another important characteristic of the sodium channel

 Therefore, it usually is not possible for the sodium channels to open

• In resting state : the potassium channel is closed, & potassium ions

Thus, the decrease in sodium entry to the cell and the

two other types of ions must be considered:

1. Impermeant anions inside the nerve axon.

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