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ACh Receptors
Neurotransmitter at NMJ
Occurs chemically – a chemical messenger
is used to carry the signal between the
neuron terminal & the muscle fiber
Synaptic knobs – 200 000 to 300 000
vesicles
Contain neurotransmitter: acetylcholine
(ACh)
ACh binds with nicotinic cholinergic receptor
at the post-synaptic membrane
Small amount of ACh that does not bind will
be loss
Neurotransmitter at NMJ
After binding with the receptor (1
– 2 msec after released), ACh will
be hydrolysed to choline and
acetate by acetylcholinesterase
Choline returns to motor nerve
terminal for ACh resynthesis
ACh recycled
Quantal Release of ACh
1. The presence of an action potential in
the terminal button triggers the
opening of voltage-gated Ca2+
channels
→ Influx of Ca2+ into the terminal button
2. Ca2+
→ triggers the vesicles to dock onto
terminal membrane
→ Also causes docked vesicles to fuse
with the membrane and the release of
Ach into synaptic cleft by exocytosis
8 8
Na+ 7
9
Neuromuscular Fatigue
25 quanta of ACh are needed to generate muscle
action potential
If the nerve that supplies the muscle is stimulated
>100 times/second,
→ rate of ACh released >> rate of ACh resynthesis
→ no impulse transmission across NMJ
→ no contraction
Known as neuromuscular fatigue
Dysfunction at NMJ
Myasthenia gravis
Autoimmune disease
Condition characterised by
extreme muscular weakness
Treat with anticholinesterase (e.g.:
neostigmine or physostigmine)
→To decrease the activity of
acetylcholinesterase
Substances Affecting the NMJ
Substances Mechanism
Alter release of ACh
• Black widow spider venom • Causes explosive release of ACh
• Clostridium botulinum toxin • Blocks release of ACh
Block ACh receptor sites
• Curare • Reversibly binds with Ach receptor
sites
Prevents inactivation of ACh
• Organophosphates (certain • Irreversibly inhibits
pesticides and military gas) acetylcholinesterase (AChE)
• Neostigmine (for treatment of • Temporarily inhibits AChE
myasthenia gravis)
Substances Affecting the NMJ
Botulinum Toxin
Powerful toxin produced by
Clostridium botulinum
Responsible for deadly food
poisoning – botulism
Now use for some specific
movement disorders
Also now used for fighting
wrinkles by cosmetic surgeons
Marketed as “Botox” –
therapeutic doses remove
wrinkles (facial rejuvenation)
Differences Between EPP and Action Potential
EPP Action Potential
• Local events, not propagated • Propagated
• No threshold • Has threshold
• No refractory period • Refractory period – absolute and
relative