Nerve and Muscle

DR/ MOHAMED HASSAN

doctorpioneer@yahoo.com
 The Nervous System
Don’t get nervous about the nervous
system
 Nerve and Muscle

 Nerve and muscle are excitable

cells i.e. able to respond to a stimulus
by changing the electrical properties
of their cell membranes.
 Neuron- basic
structural unit of the
nervous system
 Dendrites- carry
impulses towards the
cell
 Axon-carry impulses
away from the cell
 Myelin sheath
 Synaptic terminal
 Epinephrine
 Norepinephrine
 Acetylcholine
 Structure of the neuron:
Cell body:
 It contains a nucleus, cytoplasm, mitochondria,
lysosomes, endoplasmic reticulum and Golgi
complex.
 Dendrites:
 They are multiple, short and thick extensions
of the cytoplasm of the cell body. Their function is
to receive signals from other nerve cells and
conduct them toward the cell body.
 Axon (= nerve fiber) conducts impulses away
from the cell body towards its terminals. Axons
may be covered with a whitish, fatty segmented
sheath called myelin sheath. The gaps in the
myelin sheath are called nodes of Renvier.
Myelin sheath protects and electrically insulates
fibers from one another. Also, it increases the
speed of transmission of nerve impulse.
 Properties of Nerves:
 1-Excitability: It is the ability of the
nerve to respond to adequate stimulation.
 2-Conductivity: It is the ability of the
nerve to respond by conducting the nerve
impulses.
 3-Infatiguability: nerve fibers are not
fatigued by repeated stimulation.
 Resting Membrane Potential
(RMP)

 Definition:
 It is the potential difference between
the outer surface and the inner surface of
the membrane of excitable tissues (nerve &
muscle) under resting condition. The inside
of the membrane is negatively charged
with respect to the outside.
 It can be recorded by a Cathode Ray
Ossiloscope (CRO), with one electrode
placed on the outer surface and the other
one is in the inner surface of the nerve
membrane
 Causes of the resting membrane potential:

 (I) Passive Forces (93%) = Selective

Permeability Of The Membrane:
 A] Permeability of the membrane to potassium
(K+) ions is 50-70 times more than its permeability
to sodium (Na+) ions at rest.

 At rest, K+ ion concentration is high inside the

membrane than outside and the concentration of
Na+ ions is the opposite.
 Leakage membrane channels allow K+ to diffuse
outward and Na+ to diffuse inward across the cell
membrane.
 However, the cell membrane is more permeable
to K+ than to Na+ so, + ve ions are lost from inside.
 B] The membrane is not permeable
to the negatively charged proteins,
organic phosphate and sulfate ions.
So, negatively charged molecules are
retained inside.
 (II) Active force (7 %) = Na+-
K+ Pump.
 Na+ - K+ pump acts during rest
to share in building and stabilizing
RMP by pumping 3 Na+ to the
outside and 2 K+ to the inside
 It is electrogenic pump that
requires energy provided from ATP by
the activity of Na+ - K+ ATPase
enzyme.
 Action Potential

 Definition:
 It is the change
in the membrane
potential of an
excitable cell
(nerve or muscle)
in response to
stimulation by
threshold stimulus.
Phases of Action Potential and Its
Ionic Basis:

 Latent period:
 Isopotential interval represents the time
needed by the stimulus to travel along the axon to
reach the recording electrode.
 Depolarization phase:
 At the beginning of action potential, the
depolarization is slow and when the membrane
potential reaches (-55 mv) the firing level is
reached, the rate of depolarization increases
markedly and the membrane potential overshoots
beyond the zero level and become (+35 mv).
Reversal of polarity occurs = inner surface of
the membrane becomes positive in relation to
outside. The magnitude of action potential=105
mv.
 Repolarization phase:
 At the end of depolarization, the membrane
potential returns back to the resting level.
 After 70% of repolarization, the rate of
repolarization becomes more slow (=after
depolarization).
 Then, the membrane potential become more
negative (-ve) than original resting membrane
potential (=after hyperpolarization)
 Finally, the resting membrane potential (RMP)
is restored.
 Excitability ChangesDuring Action
Potential
 Absolute refractory period (ARP):
 During this period, the nerve
excitability is completely lost=zero= 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
the upper 1/3 of repolarization.
 Relative refractory period (RRP):
 During this period, nerve
excitability is only partially recovered,
thus stronger stimulus than normal is
required to excite nerve.
 It corresponds to the remaining
part 2/3 of the descending limb of
repolarization.
Neuromuscular
Transmission
 The action potential in a motor neuron is
rapidly propagated from the central
nervous system (CNS) to the skeletal
muscle along the large myelinated fiber
(axon) of the neuron.
 As the axon approaches a muscle, it divides
into many terminal branches and loses its
myelin sheath.
 Each of these axon terminals forms a
neuromuscular junction.
 The axon terminal is enlarged into a knob
like structure (the terminal button), which
fits into a shallow depression or groove in
the underlying muscle fiber
 Mechanism of Neuromuscular
Transmission:
 Transmission of impulses from the motor nerve to
the muscle is carried out chemically by acetyl
choline.
 It include 3 steps:
 - Release of acetyl choline.
 - Depolarization of the MEP.
 - Destruction of acetyl choline.
 Release of acetyl choline:
 When nerve impulse ( action potential ) reaches the
axon terminal of a motor neuron causes
opening of voltage-gated Ca2+ channels
Ca2+ diffuses to the interior of the axon terminal
 release of acetyl choline (from the vesicles by
exocytosis) into the synaptic space.
 Depolarization of motor end plate:
 The released acetyl choline binds to acetyl
choline receptor sites, present on the
motor end plate, causes opening of ligand-
gated Na+ channels → depolarization of
the motor end plate, which is local
potential, known as the end plate potential
( EPP ).

 In turn, this end plate potential initiates an

action potential at the muscle membrane
→ which become conducted along the
muscle fiber → initiates muscle contraction.
 Destruction of acetyl choline:
 - After performing its action, acetyl choline
is then removed from the synaptic cleft by
acetyl cholinesterase enzyme, which is
present in high concentration at the
neuromuscular junction.
 - Removal of acetyl choline terminates EPP,
thus, no more action potentials are initiated
in the muscle fiber.
 Drugs & chemicals that affect transmission at
the neuromuscular junction:

 Inhibit transmission at the neurouscular

junction:

 A- Block acetyl choline receptor sites:

 e.g. Curare:
 - competes with acetyl choline for the acetyl choline
receptor sites.
 - Large dose of curare death from respiratory
paralysis caused by an inability to contact the
diaphragm.

 * D-tubocurarine is used clinically in suitable doses

as muscle relaxant; to produce muscle relaxation
during surgical operation
 B- Block release of acetyl choline:
 e.g. Botulinum toxin:
 - is a bacterial toxin, responsible for
canned food poisoning.
 - decreases the release of acetyl choline by
the nerve terminals.
 - is one of the most lethal poisons known:
death is due to respiratory failure caused
by the inability to contract the diaphragm.
 Stimulate transmission at the
neuromuscular junction:

 A- Acetyl choline – like action:

 e.g. - metacholine, carbachol and
nicotine in small dose(have the same
effect on the muscle fiber as does the
acetyl choline),
 B- Prevents inactivation of acetyl
choline:
 ( by inhibiting acetyl cholinesterase )
 Neostigmine & physostigmine (short -acting):
 inactivate acetyl cholinesterase for several
hours, after which acetyl cholinesterase
becomes active again.
 Organophosphates (long- acting): e.g.
some pesticides and military nerve gases
 inactivate acetyl cholinesterase for weeks
death.
 Myasthenia Gravis:
 ( myasthenia = muscle weakness, gravis =
severe ).
 - is a disease characterized by extreme muscle
weakness because neuromuscular junction is
unable to transmit signals from the nerve fiber to
the muscle fiber.
 Cause:
 It is autoimmune disease of unknown cause; in
which the body produces antibodies against its
own motor end plate acetyl choline receptors →
the antibodies destroy some of the acetyl choline
receptors→ EPP formed is too week to
adequately stimulate the muscle fiber.
 Treatment:
 By short-term anticholinesterase drug
 e.g.,Neostigmine:
 It temporarily inhibits acetyl
cholinesterase → accumulation of acetyl
choline in the synaptic cleft→ prolongation
of the action of cetyl choline at the
neuromuscular junction → EPP of
sufficient magnitude to initiate action
potential and subsequently contraction in
the muscle fiber.
 Muscle Action Potential:
 It is like action potential in nerve fiber,
except for quantitative differences:
 Resting membrane potential is about –80
to –90 mV in skeletal muscle fiber.
 Duration of action potential in skeletal
muscle is 5 times longer than that of large
myelinated nerve.
 3- Velocity of conduction of action
potential in skeletal muscle is slower than
that in myelinated nerve.