Excitable Tisuues:

Nerve and Muscle

Dr. Taha Sadig Ahmed

1 01/04/25
• What are Excitable Tissues ? These are
tissues whose cells have high Resting
Membrane Potential (RMP) ,
• and can produce electrical
(1) NERVE impulses that
can either be local responses , or
propagated impulses that we call Action
Potentials (APs) .

2 01/04/25
What are Excitable Tissues ? These are tissues whose cells have
high Resting Membrane Potential (RMP) , and can produce
electrical impulses that we call Action Potentials (APs) .
What is the “ Membrane Potential ”(MP) of a cell ?
• It is the potential difference ( voltage ) across the cell-membrane
( i.e., potential difference between the 2 sides of the membrane ) .
• In a resting cell , it is called the Resting Membrane Potential (RMP) .
• When the cell is active , the RMP changes into Action Potential
(AP).
• The AP ( or nerve impulse ) can be conducted for long distances .
• In short:
• The MP of a resting ( inactive ) cell is called RMP = -90 mV.
• The MP of an active cell is called AP= +35 mV to 40 mV .

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 • When the cell is inactive
( resting )  we call the MP :
Resting Membrane Potential
(RMP) .
• When the cell is stimulated  a
small ( subthreshold) stimulus
can produce a Local Response (
which is graded and does not
propagated ).
Local Response • However , if the stimulus is
strong enough to exceed
Threshold Level ( the level in
MP between local response and
action potential )  an action
potential is generated .
• The AP differs from local
response in that it is (1) not
graded obeys All-or None
Law) , and (2) propagated
(conducted for long distances .
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 Ionic Channels

Q: What are the types of ion channels ? Two

types :
• (1) Leak Channels : open all the time .
Allow diffusion of ions ( Na+ or K+ ) down
their concentration gradient .
• (2) Voltage-gated channels  open only
during the action potential .

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 Na+ Nernst ( Equilibrium ) Potential
• The cell-membrane is practically considered as a semi-permeable
membrane separating the ECF from the ICF .
• Nernst , hypothetically speaking, said that if we suppose that (1) the ECF
and ICF contained ONLY sodium ion , (2) and that the cell-membrane was
freely permeable to Na+ :
  then Na+ will diffuse down its concentration gradient to the I nside of the
cell, carrying with it +ve charges , and progressively decreasing the
negativity on the inner side of the membrane .
• As this goes on and on , and as the positive charges build inside , an
opposing Electrical Potential begins to develop , tending to prevent the +ve
Na+ from entering.
• This electrical potential will grow until it becomes strong enough to balance
and counteract the concentration gradient which tends to push Na+ inside .
• When this electrical gradient ( force ) , which tends to drive Na+ outside =
the concentration gradient ( which tends to push Na+ in )  there will be no
net Na+ movement across the membrane .
• The MP potential in that case is called Nernst Potential for Na+ ( or
Na+ Equilibrium or Diffusion Potential ) = 61 mV .
• ( The charge always refers to the inside of the cell ) .

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 The Potassium Nernst ( Equilibrium ) potential
• Similarly , (1) if the ECF and ICF contained ONLY potassium ions (2) and
the membrane was freely permeable to K+
  then K+ will diffuse down its concentration gradient ( via the K+ leak
channels ) from inside the cell to outside , carrying with it +ve charges to the
outside , thereby progressively increasing the negativity on the inner side of
the membrane ( because we are losing –ve charges from inside ).
• At this goes on and on , and as negative charges build inside , an opposing
electrical potential begins to develop , tending to prevent the exit of the +ve
potassium ions .
• This electrical potential will grow until it becomes strong enough to balance
and counteract the concentration gradient which tends to push K+ outsude
• When this electrical gradient ( force ) , which tends to keep K+ inside = the
concentration gradient ( which tends to push K+ outside )  there will be no
net K+ movement across the membrane .
• The MP potential in that case is called Nernst Potential for K+ ( or
K+ Equilibrium or Diffusion Potential ) = -94 mV .
• ( The charge always refers to the inside of the cell relative to the
outside )

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• What determines the magnitude (value) of the Nernst
Potential ? The ratio of the ion concentration on the
two sides of the membrane .
• How can we determine the value of this Nernst
Potential for a given ion ?
• The value of this EMF can be determined by one of 2
ways :
• (1) It can be calculated using Nernst equation and
the concentration of the ion 
• Nernst Potential ( mV ) = +/- 61 log Conc inside/Conc
outside
• (2) Or, alternatively , it can be measured directly in
the laboratory using electrodes ( see next slide )
• The value of the Nernst Potential for K = -94 mV
• The value of the Nernst Potential for Na = +61 mV
8 01/04/25
 Measuring the MP
A pipet filled with KCl solution is impaled
through the cell membrane into the cell ICF .
This serve as the “ active “ electrode .
Then another electrode ( the “indifferent “ or
“ inactive ” electrode ) is placed outside the
cell in the ECF. They are connected by a
Voltmeter , in order to measure the voltage
difference between them ( i.e., measure the
potential difference across the membrane 
the membrane potential .).
In a resting cell , the MP is called “ Resting
Membrane Potential (RMP) “ , and its value
is = -90 mV .
In an active cell which generates action
potential the MP is called Action Potentials ,
and at the peak of AP the value of the MP is
= + 40 mV .

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 The Voltage-Gated Na+ & K+ Channels(1)
• These are channels that open
when a stimulus depolarizes the
membrane between the values
-70mV to -50 mV .
• The voltage-gated Na+
channel: has 2 gates : one near
the outside if the cell and is
called the activation gate , and
another one near the inside
called the inactivation gate .
• And this channel has 3 states :
• (1) Resting state : in the resting
cell , when the MP = RMP = -90
mV ,  the activation gate is
closed ( this prevents entry of
Na+ to the interior of the cell via
this gate ( upper left in figure ) .
10 01/04/25
 The Voltage-Gated Na+ Channel(2)
• (2) Activated state : when a stimulus
makes the MP less negative than the
RMP , and takes it to the range -70 to -
50 mV ( threshold level ) , this flips the
activation gate suddenly to the open
position  this is called the activated
state ( where both gates are open ) 
permeability to Na+ becomes
increased 500 to 5000 times  N+
pours into the cell in large amounts ,
depolarizing it .
• After one AP , the inactivation gate will
not open ( & the cell becomes
refractory ) until the MP has gone back
to the resting level ( -90mV).
• (3) Inactivated state : A few
milliseconds after the activation gate
opens , the channel becomes
inactivated : while the activation
gate is still open , the inactivation gate
is closed .
11 01/04/25
 The Voltage-Gated Potassium Channel
• During the resting state , the
gate of the potassium
channel is closed , and K+
can not enter through it .
• Shortly after depolarization ,
when the sodium channel
begins to be inactivated , the
potassium channel opens .
• Thus , the simultaneous
decrease in sodium entry
into the cell , and increase in
potassium exit from the cell
 greatly speed the
repolarization process .
12 01/04/25
 Origin of the RMP (1)
• Q: What are the factors that (1)
make the inside of the cell
negative (2) make this value of
the RMP between -90
millivolts ?
They are :
• (1) At rest , K+ leak channels
are more effective than Na+
leak channels  more K+
diffuses to outside than Na+ to
inside  i.e , the membrane is
50 -100 times more permeable
to K+ than to Na+
• ( leak channels allow passive
diffusion of ions down their
concentration gradients )

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 Origin of the RMP (2)
(2) Large intracellular
anions ( proteins ,
sulphates & phosphates )
(3) The sodium-potassium
pump ( 3Na+ pumped out
in exchange for 2 K+
pumped in ) .

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 In summary
• The diffusion potentials caused by K and Na ( in
addition to the role of intracellular anions ) give a
MP = -84 mV ;
• Then , the Na-K pump adds another -4 mV ; to
make the RMP =(-84) + (- 4mV) = -9o mV .

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 The Action Potential (AP)
( nerve impulse & muscle AP )
A/ ELECTRICAL CHANGES DURING THE
AP
(1) Resting state of the membrane potential
( MP) : the resting membrane
potential(RMP) .
(2) Depolarization phase of the AP
(3) Repolarization phase of the AP .

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 The Nerve Action Potential
(Nerve Impulse ) (1)

As mentioned before, in a resting

cell the membrane coductance to
K+> Na+(due to K+ leak channels
) & the RMP= -90 mV.
(1) A stimulus strong enough to
carry the MP to the threshold
level ( -65 mV ) causes explosive
activation of voltage-gated
Na+channel  5000 fold
increase inNa+ conductance
massive Na+inflow
depolarization. Then overshoot
( reversal of MP) occurs as the
inside of the cell becomes +ve ; &
the peak of AP is reached at +35
- +40 mV.
17 01/04/25
 The Nerve Action Potential
(Nerve Impulse ) (2)
(2) Repolarization phase is due to
delayed opening of K+channels
( Na+ channels are already
inactivated )  rapid K+
outflow the MP quickly returns
toward the resting level .
(3) In some nerves there is a
Positive After Potential, due to
continued outflow of K+, which
causes the membrane to
becomes hyperpolarized .
However , the Na+-K+ pump soon
restores the MP to the resting
(RMP) level .
18 01/04/25
 Excitability Changes During the AP (1)
Immediately after an AP there
is :
(1) Absolute Refractory Period :
where no stimulus ,
however strong , can
produce a second AP . It is
due to inactivation of Na+
channels .
(2) Relative Refractory Period :
a stimulus higher than
threshold is needed to
produce an AP . Due to
continued outflow of K+ .
ALL-or-Nothing ( None) Law :A
stimulus , if threshold,
produces a full propagating
AP. Otherwise no
19 propagating AP is produced
01/04/25
( there are no half solutions ) .
 Excitability Changes During the AP (2)
Absolute Refractory Period is
present during
depolarization and almost
the first half of
repolarization
Relative Refractory period
covers the remainder of the
action potential
ALL-or-Nothing ( None) Law :A
stimulus , if threshold,
produces a full propagating
AP. Otherwise no
propagating AP is produced
( there are no half solutions ) .
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 Types of Nerve Fibers
In both myelinated and unmyelinated
fibers impulses are propagated
( conducted ) by Ionic current Flows .
However , in unmyelinated fibers
these currents are local , and in
myelinated ones they are saltatory
( jumping )from one Node of Ranvier
to the next one .

• Myelinated Fibers : have myelin

sheath , excellent insulator ,
decreases ions flow through the
membrane .
• Ions can easily flow only at the
Nodes of Ranvier . Why ?.
• Unmyelinated nerves have no
myelin sheath : consequences ?

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22 01/04/25
  Myelin is an excellent insulator : it makes
ion flown across the membrane much more
harder than otherwise 
 decreases ion leakage ( Na+ to inside and
K+ to outside ) and loss by a factor of 5000
times , hence it makes the myelinated nerve
 (1) more economical ( because it prevents
loss/dissipation of membrane charge
{RMP } , which is due toaccumulation of Na+
outside and K+ inside ) ,and
(2) faster-conducting ( because ionic
currents need to “ jump ” over relatively long
distances ( from one node of Ranvier to the
23
next ) . 01/04/25
 Saltatory Conduction ( propagation ) of
APs in myelinated nerves
(A) Myelin sheath is absent at the Nodes of Ranvier ,
each of which is about 2 – 3 microns ( micrometer )
wide.
 Therefore ionic flow ( & consequently flow of ionic
currents ) can easily take place only at the Nodes of
Ranvier .
(B) Moreover , voltage-gated channels are present only at
the Nodes of Ranvier .
• Therefore , APs can develop only at the
Nodes of Ranvier  Where
(1) ions can relatively easily flow in & out
(2) there are voltage-gated channels .
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 Point-to-Point ( Contiguous , Continuous , )
Conduction in Unmyelinated Nerves
(A) Myelin does not completely wrap around & cover the axon

• Consequently , ionic flow can take place anywhere
along the membrane at much less difficulty than in
myelinated fibers .
(B) Voltage-gated channels are present all along the
membrane
• Consequently an AP can develop anywhere along the
membrane under suitable conditions ( if the threshold
potential is reached ).
( N.B. in myelinated nerves threshold potential can only be
reached at the Nodes of Ranvier ).

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 Propagation ( Conduction ) of AP :By Circular Current
Flows
In unmyelinted fibers : by Point-to-
Point Conduction ( also called
Contiguous Conduction ) by Local
Circular Currents, & conduction
velocity(CV) = 0.25-3.0 m/s.
In myelinated nerves : Saltatory
Conduction ( Long Distance
Currents)  impulses jump from
one node of Ranvier to another)
which is (1) Faster (2) Economical :
conserves energy for the axon .
Point-to –Point conducti
in unmyelinated nerve

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NB : In the laboratory ,
if we electrically
stimulate a nerve
fiber at a point , the
AP travels in both Axon hillock
direction .This is o, of
course , NOT a
normal way , but
artificial stimulation .
However , normally
the AP travels along
the nerve fiber along
one direction only :
from its origin at the
axon hillock ( in the
cell-body )  towards
the nerve ending
( terminal ) . Nerve terminal
( ending )

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28 Under Artificial condition of electrical stimulation
01/04/25
in the laboratory
•END

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