Excitable Tissues

DR. Khadeejah alsolami

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 Excitable Tissues
Nerves and muscles are excitable tissues because
they are able to respond to a change in surrounding
environment (called stimulus) by changing the
electrical properties of their cell membrane and
generating impulses, and these impulses are used
to transmit signals along the nerve or muscle
membranes.

DR. Khadeejah alsolami

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 “Nerve”
Nerve cell (neurons): are the
structural
and functional units of the
nervous system.
1 - The Cell
Body
2 - Dendrites
3- The Axon
4- Axonal
Terminals
DR. Khadeejah alsolami
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 Myelin Sheath:

Many nerve fibers are

covered with a whitish,
fatty (protein-lipid)
sheath called the
myelin sheath.
Myelin protects and
electrically insulates
fibers from one
another, and it
increases the speed of DR. Khadeejah alsolami 4
 Physiology of Cell
membrane:

The fluid which lies

outside the cell
membranes (ECF),
differ in composition
from that inside the
cell (ICF).

DR. Khadeejah alsolami

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The cell membrane consists almost of a lipid bilayer, with
large number of proteins molecule. The cell membrane act
as a barrier for the movement of most water molecules
and water soluble substance between ECF and ICF.
Membrane potential
caused by
differences in the
ions concentration on
the two sides of the
membrane caused by
ion diffusion from its
high concentration
area to a lower DR. Khadeejah alsolami
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concentration area.
diffusion of solute from
its high concentration
area (left) to a lower
concentration area
(right). Movements of
solutes or ions is due to
concentration
gradients.
DR. Khadeejah alsolami
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 Ion Channels:
Plasma membranes are covered with a variety of ion
channels made up of membrane proteins. Some of these
channels are:
1. Leakage channels (passive):
• Are always open.
• Allow free movement of certain ions or molecules.
• Tube-shaped channels from the extracellular
• (ECF) to the intracellular (ICF) ends.
• Highly selective for the transport of one or more ions.

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 2. Gated channels
(active):
Gated channels have a molecular “gate”, usually one or
more protein molecules that can change shape to open or
close the channel in response to various signals
a) Chemically-gated
channels (Ligand):
Open when the
neurotransmitter binds e.g.
Acetylcholine
b) Voltage-gated
channels: the gate
responds to the electrical
potential changes 9
 Membrane
 potentials:
Polarized state (Resting membrane potentials):

Definition: it is the difference in potential between the outer

surface and the inner surface of the membrane of excitable tissues
(nerve & muscle) under resting condition.

The RMP of a nerve fiber is around –70 mv. That means, the potential
inside the nerve fiber is 70 millivolt more negative than the potential
in the extracellular fluid outside the fiber.

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 Depolarized state (depolarization): It is the
reduction in membrane potential negativity (–60, –50, –
40, ….+10, +20 …. mv), the inside of the membrane
becomes less negative than the resting potential.

 Hyperpolarized state (hyperpolarization): It is the

increase in membrane potential negativity (–90, –100,
…..mv), the inside of the membrane becomes more
negative than the value of the resting potential.
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 Factors determine
RMP:
1. Passive Transport:
•Selective permeability to potassium ions through
Potassium “leak” channel.
•These K+ leak channels may also leak Na+ ions slightly
but are far more permeable to potassium than sodium
(about 100 times).
•The membrane is not permeable most of the negatively
charged anions inside the cells especially proteins. This
result in entrapment of protein anions inside the cell.

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2. Active Transport
of Sodium and
Potassium Ions
(Na+- K+ Pump):
•This pump continually
transports 3 sodium ions
to the outside of the cell
and 2 potassium ion to
the inside. Because more
positive charges are
pumped to the outside
than the inside, which
causes a negative
potential inside the cell 13
Action
potential LOREM IPSUM

LOREM IPSUM LOREM IPSUM

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 Action
Definition: it is potential
a transient reversalin the membrane
polarity of an excitable cell (nerve or muscle) in response
to threshold
Phases andstimulus.
ionic basis:
[Link] phase (Latent
period):
•It is the period from applying the
stimulus until the response is
produced. This is the resting
membrane potential before the
action potential begins.
•The membrane is “polarized”
during this stage –70 mvs. 15
2. Local excitatory state:
•It is the period of depolarization where the
membrane
potential changes from -70 to– 55 mv.
•It is caused by opening of voltage sensitive
sodium channels.
•During this period the amount of depolarization
is proportionate to intensity of the stimulus and if
the potential does not reach – 55 mv the potential
produced remain local not propagated.

3. Depolarization
phase:
•It is the ascending limb of the spine or the
upstroke where membrane potential is
changed from -55 to +35.
•At this stage, opening of voltage gated 16
sodium channels allows positively charged
[Link]
phase:
•It is the descending limb of the
spike or the down stroke where the
membrane potential is returning to
its resting value.
•The sodium channels begin to close
5.
and the potassium channels open.

Hyperpolarization
:
some of the voltage gated K+
6. The
channels resting
are still open with slow
state:
return to the close state.

during which the Na+-K+

pump acts to restore ionic
distribution. 17
–55

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 Excitability changes during action
potential:
• Absolute refractory period
(ARP):
During this period, the nerve excitability
is completely lost (I.e. no stimulus can
excite the nerve whatever its strength).
It corresponds to the depolarization
phase and early part of repolarization
(ascending limb of depolarization and
upper 1/3 of repolarization). It is due to
inactivation of volt sensitive Na+
• channels
Relative refractory
during this period. period
(RRP):
this period, nerve excitability is only
partially recovered thus stronger
stimulus than normal is
required to excite nerve. It
correspond to the remaining part 2/3 of 19
the descending limb of repolarization. It
 Local potential:
It is a local partial non-propagated change in the membrane potential.
The local response may be produced in neurons with subthreshold stimuli (local
excitatory state).
Action potential Graded potential (local response)
Sub-threshold
Threshold stimulus
Its amplitude is 10 mv
Its amplitude is 100 mv
duration is long up to 1 minute
short duration 2-5 ms

Volt-sensitive sodium channels Ion channel involved

Doesn’t obey
Obeys All or Non
Non propagated
Propagate
Excitability high
Excitability varies
Summated
Not summated
No refractory periods
Has Refractory periods

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 All or None Low:

 If a single nerve fiber is stimulated with an inadequate (sub-threshold)

stimulus no action potential only a local non-propagated change in the
membrane polarity.

 Is a single nerve fiber is stimulated with an adequate (threshold) stimulus, an

action potential will result.

 If a single nerve fiber is stimulated with a supra-threshold stimulus, an action

potential will result which has the same characteristic.
 NOTE: Action potential has fixed amplitude independent of the strength of
the stimulus above the threshold value. Increasing the intensity of
stimulation can increase the frequency of identical action potential.

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It states that with the
threshold stimulus a full
action potential is
produced. With stimuli
higher than the threshold
no change in action
potential produced. With
stimuli below the threshold
no action potential is
produced.

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 Propagation (conduction):

Conduction in
unmyelinated fibers:
The action potential moves
along the axon as a wave of
depolarization traveling away
from the cell body. i.e.
conduction occurs
continuously from point to
the next point, so it is slow
about 0.5-2 m/sec.

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 Conduction in myelinated
fibers:
Myelin sheath is deposited around
the axons by Schwann cells and
oligodendrocytes which leaving
small areas of axon uncovered and
called “nodes of Ranvier”. Myelin
sheath contains a lipid substance
which decreases ion flow through the
membrane. Therefore, action
potentials occur only at nodes of
Ranvier. The nerve impulse jumps
along from node to the next node of
Ranvier which is the origin of the
term “salutatory conduction”.

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 Importance of salutatory conduction:
 Increases the velocity of nerve transmission in myelinated fibers
(100 m/sec).
 Conserves energy.
 Rapid repolarization.
Factors affecting conduction velocity:

 Type of nerve fiber:

o Fibre diameter the velocity of conduction is directly proportional to nerve
fiber diameter.
o Thickness of myelin sheath. The thicker the fiber, the higher the velocity of
conduction
 Temperature also affects conductivity as the increase in temperature
increases conductivity.

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 Types of nerve fibers:

Type A: has the largest diameter

and highest velocity of conduction.
Subtypes are alpha, beta, gamma,
and delta.
Type B: has a moderate diameter
and moderate velocity of
conduction.
Type C: has the smallest diameter
and the lowest velocity of
conduction.

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Muscular
Tissue LOREM IPSUM

LOREM IPSUM LOREM IPSUM

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Muscular
Tissue

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 Physiological anatomy of skeletal muscle:

Muscle Fascicle Muscle Fiber (muscle cell) Myofibril Thin and thick filaments
(actin and myosin filaments).

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Myofibril contains the main contractile proteins which are arranged as:
• Thick filaments (myosin): It is composed of
o Myosin tail.
o Myosin head (cross-bridges): which contains:
 an actin-binding site .
 ATP binding site.
 Catalytic site that hydrolyzes ATP.
• Thin filaments: which made up of:
o Actin: which has specific sites for binding with the cross-bridges of the myosin
filaments. [active sites].
o Tropomyosin: binds to actin in order to covers the active sites on the actin under resting
conditions.
o Troponin: located along the tropomyosin molecules which has a regulatory function by
binding to Ca2+.
• Elastic filaments (Titin): it acts as a framework that lines up the actin and myosin filaments.

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Figure : Thick and thin filaments.

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Figure : thin filaments.

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 What is Sarcomere??
Sarcomere is the smallest functional (contractile) unit of muscular tissue. It is the portion of the myofibril that lies
between two successive Z lines (Z-discs). The thick filaments are arranged in the middle of the sarcomere. The thin
filaments are arranged at sides of the sarcomere and overlap part of the thick filaments. The amount of overlap between
thick and thin filaments determines how much force the muscle will develop when stimulated.

Figure : Sarcomere.

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Figure: Sarcomere.

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Transverse T-Tubules:
It is an invagination of the surface of the muscle membrane and contains extracellular fluid. T-tubules help to carry
electrical impulses deep within a muscle fiber and this allows the impulse to be brought very close to the sarcoplasmic
reticulum throughout the fiber.

Figure :
A portion of myofibril shows
T-tubules and sarcoplasmic reticulum.

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 Neuromuscular Transmission

Neuromuscular transmission: Is transmission of impulses from motor neuron to skeletal muscle fibers.

Neuromuscular junction: it is the place where the motor neuron axon connects to the muscle fiber.
It contains:
• Axon of motor neuron:
contains acetylcholine (ACh)
vesicles.
• Motor end plate: this is a
thickened membrane of muscle
fiber and rich in Ach receptors.
• Synaptic cleft: it is the
extracellular space between the
nerve terminals and muscle
membrane which contains the
enzyme acetylcholine esterase
(AChase).
Figure: Neuromuscular junction.

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Steps of neuromuscular transmission:

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 Properties of Neuromuscular Transmission:

1. It is unidirectional.
2. There is a delay of about 0.5 msec.
3. Easily fatigued as a result of
repeated stimulation due to
exhaustion of Ach vesicles.
4. Effect of Ions: Ca++ increases
release of Ach, while in presence of
excess Mg++ the release of Ach is
greatly decreased.

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 The neuromuscular junction is affected by many drugs

 Drugs that inhibit neuromuscular transmission:

o Botulinum toxin: it inhibits the release of Ach.
o Curare: it blocks the transmission by competitive inhibition at the
cholinergic receptors.
o Nicotine in large dose and succinylcholine: produce persistent
 Drugs that
depolarization. enhance (facilitate) neuromuscular
transmission
o Nicotine in small dose: stimulates the nicotinic receptors.
o Cholineesterase inhibitors:
• Reversible cholinestrase inhibitors: like neostigmine.
• Irreversible cholinestarse inhibitors: Organic phosphorus compounds like
DFP

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Figure :
ACh is released from axonal terminal
of a motor neuron to the synaptic cleft.
ACh binds to the ACh receptors at the
motor end plate and that stimulates sodium
channel opening and sodium influx.
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 Cross bridge cycle
a) Resting state: In the relaxed state, ATP bound to
the myosin head is partially hydrolysed to ADP
+ Pi. (M ADP Pi)
b) In the presence of the elevated myoplasmic
calcium, myosin binds to actin.
c) Hydrolysis of ATP is completed causing a
conformational change in the myosin molecule,
which pulls the actin filament towards the
center of the sarcomere.
d) A new ATP binds to myosin causing release of
cross bridge. Partial hydrolysis of the newly
If the myoplasmic calcium levels are still elevated
bound ATP recock the myosin head which is now
the cycle repeats. If myoplasmic calcium are low
ready to bind again and again.
relaxation occurs.
NB: Shortage of ATP during muscle contraction stops
the cycle in step c with formation of permanent
actin myosin complexes as occurs during death
(rigor mortis).
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Figure : action potential transmission in skeletal muscles.

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Figure : Cross bridge cycle
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Sliding filaments theory of
contraction:
During muscle contraction the thin actin
filaments slide over the thick myosin filaments.
Step 1: Binding: myosin head attached to actin.
(High energy ADP +P)
Step 2: Bending (Power stroke): tilting of
myosin head by 45°.
Step 3: Detachment: the cross bridge detaches
when a new ATP binds to myosin.
Step 4: Binding: Rising of myosin head occurs
when ATP splits to ADP+P.

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 Factors affecting muscle contraction:
1- Initial muscle fiber length (length-tension relationship) “Starling’s Low”:

This diagram demonstrates that maximum contraction occurs

when there is maximum overlap between the actin filaments
and the cross-bridges of the myosin filaments, and supports the
idea that the greater the number of cross-bridges pulling the
actin filaments, the greater the strength of contraction.

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2. Type of muscle fiber.

”Type II “Fast
Type I “slow” “ red
”fibers Type IIa Type IIb
”red fibers “ ”white fibers “

Glycolytic
ATP source Oxidative Oxidative
“anaerobic
”oxidation

ATP release Slow Fast Fast

Contraction velocity Slow Fast Fast

Mitochondria many many Few

Low “ maintaining
Fatigue intermediate High
”posture

Myoglobin ”High “ red fibers high Deficit

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3. Mechanical changes: Isotonic contraction Isometric contraction
Muscle shortening No muscle shortening during contraction

Fixed tension Max tension

Against a light or moderate loads i.e. do

Against a heavy load i.e. no work
work
Mechanical efficiency 40% -50% Mechanical efficiency = 0

i.e. part of energy converts to work, and others as heat .i.e. all energy is lost as heat

.loss

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 Myasthenia Gravis
It is a condition characterized by extreme muscular weakness. It is an autoimmune
condition in which the body produces antibodies against its own motor end-plate nicotinic
ACh receptors. These antibodies destroy the receptors. So, not all of the released ACh
molecules are able to find a functioning receptor site to bind. As a result, much of the ACh
is destroyed by AChE without ever having an opportunity to interact with a receptor site
and contribute to EEP.
Treatment: administration of a drug that reversibly inhibits AChE temporarily to
increase the level of ACh at the motor end plates (neostigmine) or by inhibiting the
immune response by immunosuppressant drugs.

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Best of luck

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