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Neuromuscular Junction
and
Neuromuscular transmission

Neuromuscular junction
 Skeletal
 Large

muscles innervated

motor nerve fibers

 Anterior

horns of spinal cord
 One junction per fiber

Neuromuscular

junction

Neuromuscular junction








A region of close contact between a neuron &
a muscle is a functional continuity, no
anatomical continuity
Places where motor nerve fibers make
functional contact with muscle fibers,
 usually located near mid point & action
potential spreads on both sides
The point where nerve reaches the muscle,
myelin sheath is absent and fine filaments
pass to the sensitive area on the surface of
muscle fibers

Motor end plate


Area of muscle cell membrane in region of NMJ

Motor end plate


The set of muscle fibers innervated by all the
branches of axon of a single motor neuron
 (3 – several hundred sk muscle fibers)



Each muscle fiber innervated by one motor end plate
and each motor neuron has many motor end plates

Motor end plate


The large Myelinated nerve fiber
forms a complex of branching nerve
terminals
 invaginate

into the surface of the muscle fiber
 But…
...

 Entire structure is called the motor end plate
...


40 nm vesicles formed in GA of cell body- Motor neuron
Vesicles transported---axoplasmic streaming to nerve terminal
Acetylcholine synthesized in terminal parts of nerve - stored
At rest (MEPP) occasional fuse
Action potential opens calcium channels
Calcium inside terminal rise x 100
Vesicles fusion increased X 10,000

Exocytosis of acetylcholine – 125 vesicles/AP
...
65 nm – Allows




Sodium
Potassium and
Calcium to pass



PRACTICALLY SODIUM PASSES MOST
 Sodium more in
ECF
 Potassium more
ICF



END PLATE POTENTIAL



INITIATES ACTION POTENTIAL

End Plate Potential and Excitation of
the Skeletal Muscle Fiber

Safety Factor for Transmission at the
Neuromuscular Junction;
Fatigue of the Junction







Each impulse causes about three times as much end
plate potential as that required to stimulate the muscle
fiber
...

Stimulation greater than 100 times per second for
several minutes
Diminishes the number of acetylcholine vesicles so
much that impulses fail to pass into the muscle fiber
...


Duration of AP:
1 to 5 milliseconds (about 5 times
as long as in large myelinated nerves)



Velocity of conduction:
3

to 5 m/sec

 (about

1/3 of that in large myelinated

nerve fibers)
...




Drug that stimulate NMJ by
inactivation of Acetyl cholinesterase
...

 Methacholine,
 Carbachol
 Nicotine
...



Neostigmine ,



Physostigmine and



Diisopropyl fluorophosphate
...
means muscular weakness



GRAVIS…
...
drooping of eyelid
 Diplopia……… Double vision
Difficulty in chewing, swallowing, speaking, limb
movement
Respiratory muscles weakness – Death

PTOSIS

Myasthenic patient

Clinical presentation


Progression of disease




Mild to more severe over weeks to months
 Usually spreads from ocular to facial to bulbar to truncal
and limb muscles
 Often, symptoms may remain limited to EOM and eyelid
muscles for years

Remissions
Spontaneous remissions rare
 Most remissions with treatment occur within the first three
years


Clinical presentation


Co-existing autoimmune diseases
 Hyperthyroidism
 Occurs

in 10-15% MG patients

 Rheumatoid
 Scleroderma
 Lupus

arthritis

Management of Myasthenia gravis


Anticholinesterases



Immunosuppressive therapy



Plasma exchange



Immunoglobulins



Thymectomy



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