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Chapter 7
neuromuscular junction

DR FARZANA MAJEED
AP PHYSIOLOGY

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neuromuscular junction

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 The Motor End Plate
•Myelinated nerve
fiber is seen Striated muscle
reaching the fibers
surface of
muscle cells that
have been teased Axon
apart. Motor End Plate

•Terminal region
branches From R.A. Bergman,
extensively to A.K. Afifi and P.M.
Heidger
form the Virtual Hospital: Atlas
of Microscopic
neuromuscular Anatomy
University of Iowa
junction.
 Sequence of Events in Neuromuscular
Transmission (1)
Presynaptic Events
1. Action potential (AP) is initiated in the presynaptic
motor neuron (MN) and invades the endplate region
2. Depolarization of MN terminal boutons, resulting in the
opening of voltage-dependent calcium channels
3. Influx of Ca2+, down its concentration gradient
4. Rise of intracellular free [Ca2+] initiates fusion of
vesicles containing acetylcholine (ACh) to the membrane
of the terminal boutons, resulting in exocytosis of ACh
5. Diffusion of ACh across synaptic cleft to the muscle
cell
 Sequence of Events in Neuromuscular
Transmission (2)
Postsynaptic Events
6. Binding of ACh to nicotinic ACh-receptors at endplate
7. Receptor binding causes opening of cation channels,
leading to influx of Na+ (ACh is then degraded by
acetylcholinesterase present in the synaptic cleft)
8. The resulting depolarization of muscle cell membrane at
the endplate is referred to as the endplate potential (EPP)
9. The local depolarization causes adjacent regions to be
depolarized, causing an AP in the muscle cell membrane
10. AP spreads out in all directions from the endplate,
propagates along muscle cell, initiating contraction
 Motor End Plate
Electron micrograph of nerve terminal
Postsynaptic Presynaptic
terminal, with
region of the many small
skeletal vesicles
muscle, with containing ACh
mitochondria
and contractile
filaments
apparent in the From Alberts, Bray,

cytoplasm Lewis, Raff, Roberts

and Watson,
500 nm Molecular Biology of
the Cell, 2nd edition
 Motor End Plate (continued)

Each vesicle
contains ~5000
ACh molecules.
1 vesicle=1
quanta
Each vesicle is
~50 nm
diameter

Postsynaptic membrane: Synaptic cleft between

Clusters of nicotinic ACh nerve and muscle cells
receptors in the junctional Size? A 50 to 100 nm
folds gap.
 Exocytosis at the Terminal
Boutons
Resting nerve with
abundant vesicles
Synaptic cleft is
50 to 100 nm

Stimulate nerve Time for diffusion

and observe fusion of ACh is ~0.5 ms
of vesicles with
membrane.
Vesicle exocytosis
releases ACh into
synaptic space
Destruction of the Released Ach

The acetylcholine, once released into the

synaptic space, continuous to activate
the Ach receptors as long as it persists
in the space. However, it is soon
destroyed by the enzyme
acetylcholinesterase & a small amount
diffuses out of the synaptic space.

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End Plate Potentials
It is the local change in the muscle membrane due to influx
of sodium ions. Action potential is generated when end plate
potential attains critical level.
• From mini-EPP, to summation and EPP to Action Potential

Schematic
Record
courtesy
of T. Membran
Stavraky e
potential
of muscle
Stimulate nerve
Vm
Vm Vm
0.5
5 5
mV Stimulate
mV mV
Stimulate nerve
Miniature EPP
nerve EPP brings membrane
(spontaneous, 1 vesicle EPP
aka 1 quantum) to threshold and initiates
(evoked, ~200 quanta) action potential
Factors Effecting Transmission at
NMJ
1. Drugs that have action like Ach on
NMJ include methacholine, carbachol &
nicotine.
3. Drugs that stimulate the NMJ by
inactivating acetylcholinesterase
include neostigmine, physostigmine &
diisopropyl flurophosphate. This causes
muscle spasm. The last drug is used as
powerful nerve gas poison. Clinically
neostigmine is used for the treatment
of myasthenia gravis

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3. Lack of calcium ions or excess of
magnesium ions in the ECF or presence of
botulinum toxin ( a bacterial poison) lead to
decrease in release of Ach.
The action these drugs persists for many
minutes to several hour’s because they are
not destroyed by the enzyme cholinesterase
or are destroyed slowly. This results in
muscle spasm.

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4. Drugs that block transmission at NMJ
include curariform drugs e.g. D-
tubocurarine.
These are the drugs which block the action
of Ach on receptors sites.
Clinically this drug is used along with general
anesthetics to relaxes anterior
abdominal muscles during abdominal
surgery.

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Excitation-Contraction Coupling

• Sequence of events that links the nerve

impulse and skeletal muscle contraction
• Motor Neurons – stimulates skeletal muscles
• Excitatory effect
• When a skeletal muscle cell receives input
from a motor neuron, it depolarizes
• Depolarization causes the muscle cell to
fire an action potential
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Sources of energy for muscle contraction:

 The concentration of ATP in the muscle

fiber, about 4 milli molar, Which is
sufficient to maintain full contraction
for only 1-2 seconds at the most.
 The ADP is rephosphorylated to form
new ATP within another fraction of a
second, which allows the muscle to
continue its contraction. There are
several sources of the energy for this
rephosphorylation.

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Sources of energy for
rephosphorylation:
• 1st source is phosphocreatine which is five
times greater than ATP. Both ATP &
Phosphocreatine are sufficient to provide
full contraction for 5-8 seconds.
• 2nd source of energy is anaerobic glycolysis.
It maintains contraction for several seconds
& some times more than a minute.
• 3rd source is oxidative metabolism of CHO,
fats & proteins. This is responsible for
sustain contraction muscle.

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