Pharmacology of the NMJ junction

Question 1

What are the steps of synaptic transmission?

Answer 1

Synthesis and packaging of neurotransmitter (usually) in presynaptic terminals

Na+ action potential reaches terminal

Activates voltage gated Ca2+ channels

Triggers Ca2+-dependent exocytosis of pre-packaged vesicles of transmitter

Transmitter diffuses across cleft and binds to ionotropic and/or metabotropic receptors to evoke postsynaptic response

Presynaptic autoreceptors inhibit further transmitter release

Transmitter is (usually) inactivated by uptake into glia or neurons

Transmitter is metabolised within cells

Question 2

What are the ways to inhibit transmission?

Answer 2

Inhibit choline transporter (e.g. hemicholinium)

Block voltage gated Ca2+ channels (e.g. black widow spider venom)

Block vesicle fusion (e.g. botulinium toxins)

Use non-depolarising nicotinic receptor blockers (e.g. d-tubocurarine)

Use depolarising nicotinic receptor blockers (e.g. suxamethoneum = succinylcholine)

Question 3

What are ways to potentiate transmission?

Answer 3

block acetylcholinesterase (e.g. eserine)

Question 4

Clinical applications?

Answer 4

Non-depolarising or depolarising blockers used for paralysis during:
Surgical procedures
Electroconvulsive therapy
Controlling spasms in tetanus

Botulinum toxin
Treating muscle spasms
Cosmetic procedures

Anti-cholinesterases
Treating myasthenia gravis
Reversing action of non-depolarising blockers
Countering botulinum poisoning