Neuromuscular Junction
By:
Dr Asma Jabeen
Learning Objectives
At the end of this lecture the students should be
able to:
•Describe the physiological anatomy of
neuromuscular junction.
•Explain the mechanism of neuromuscular
transmission.
•List and discuss the properties of neuromuscular
transmission.
•Relate this knowledge to the pathophysiology of
myasthenia gravis.
Physiologic anatomy of NMJ
Motor End plate
 Motor endplate
 Synaptic gutter
or trough
 Synaptic cleft
 Subneural
folds
 Acetylecholine
vesicles
Acetylcholine formation and release
 Vesicles,40nm formed by golgi apparatus in
cell body of motor neuron
 Vesicles transported through axoplasm to NMJ
 About 300,000 of small vesicles collect
 Ach synthesized in cytosol, transported to
vesicle, stored in highly conc. form
Secretion of Acetylcholine by
nerve terminal
 About 125 acetylcholine vesicles rupture with
each action potential
 After a few msec, Ach is split by
acetylcholinestrase, choline is reabsorbed into
neural terminal for reuse.
 Within a few seconds, new vesicles are
formed by breaking of coated pits to the
interior with the help of “clathrin”
Effect of Acetylcholine on post synaptic
Muscle fiber membrane
Only sodium ions flow through acetylcholine
gated ion channel !!
 0.65nm diameter
 Negative potential inside pulls positively
charged sodium ions
 Negative potential inside prevent efflux
of potassium ions
Fate of acetylcholine in synaptic space
 Most is destroyed by acetylcholinesterase
 Small amount diffuses out of
synaptic space
Properties of neuromuscular
transmission
End Plate Potential
A local positive potential change inside
the muscle fiber membrane by influx of
Sodium ions is called End Plate Potential.
50 to 75mv in the positive direction.
This end plate potential initiates action
potential that spreads along the muscle
membrane and cause muscle contraction.
End Plate Potentials
Safety factor for neuromuscular
transmission
Each impulse causes three times as much
end plate potential as that required to stimulate
muscle fiber
high safety factor
Fatigue of neuromuscular junction
Stimulation of nerve fiber at rates
greater than 100 times/sec for several
minutes diminishes the number of
acetylcholine vesicles so much that impulses
fail to pass into the muscle fiber. This is
called fatigue of neuromuscular junction.
Drugs affecting transmission at
neuromuscular junction
1.Drugs stimulating the muscle fiber by
acetylcholine like actions
The actions of these drugs persist for many
minutes to several hours as these are not
destroyed by acetylcholinesterase.

Methacholine
 Carbachol
 Nicotine
2. Drugs stimulating neuromuscular junction
by inactivating acetylcholinesterase:
 Neostigmine
 Physostigmine
 Diisopropyle fluorophosphate



With each successive nerve impulse, additional
Acetycholine accumulates and stimulate muscle
fiber, causing muscle spasm
Neostigmine and physostigmine inactivate
acetylcholinesterase for several hours.
Diisopropyl fluorophosphate is a nerve gas poison which
inactivates acetylcholinesterase for weeks.
3. Drugs that block transmission at
Neuromuscular junction:
These drugs prevent the passage of impulses
from the nerve ending into the muscle.
 D-tubocurarine..blocks the action of
acetylcholine on the acetylcholine receptors, thus
preventing sufficient increase in permeability of
the membrane channel to initiate an action
potential
 Botulinum toxin
Myasthenia Gravis
It is an autoimmune disease in which
patient develops immunity against their
own acetylcholine-activated ion channels
 Muscle paralysis occurs because of
inability of the neuromuscular junctions
to transmit enough signals from nerve
to muscle
 End plate potentials developed are
too weak to develop action potentials
 Antibodies against acetylcholine gated
channels are found in patients
 Patient may die of respiratory paralysis
Treatment:
Administration of neostigmine or
some anticholinesterase drug.
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