The neuromuscular junction Flashcards
The neuromuscular junction
A specialised synapse between a motor neurone and a muscle cell, providing rapid and reliable neurotransmission.
Features of the presynaptic membrane
Has lots of vesicles containing neurotransmitters.
Features of the postsynaptic membrane
Highly folded, has a high density of nACh recpetors and voltage-gated Na+ channels.
Events at the presynaptic membrane
- action potential reaches the presynaptic terminal
- depolarisation opens voltage-gated Ca2+ channels
- Ca2+ influx detected by binding to synaptotagmin
- triggers fusion of vesicles with pre-synaptic membrane
- acetylcholine released by exocytosis
Events at the postsynaptic membrane
- large amounts of acetylcholine cross the synaptic cleft
- acetylcholine binds to nicotinic ACh receptors on the postsynaptic end plate membrane
- opens ligand-gated ion channels
- influx of Na+ triggers depolarisation
End-plate potential
The depolarisation achieved due to the binding of ACh at the postsynaptic membrane. EPP= -20mv
- passes the threshold
- initiates an action potential
- decays as it moves away from the end plate (nAChRs absent away from synapse)
Properties of the EPP
- presynaptic AP to EPP takes ~1ms
- generated by ligand-gated channels, opening voltage-gated channels (action potential)
- very large compared to most synaptic potentials (many ACh vesicles released, high density of nAChRs)
- threshold for AP generation easily passed (high density of voltage-gated Na+ channels)
Postsynaptic action potential
Depolarisation invades T (transverse) tubule system, allowing transmission of the action potential deep into the muscle fibre to separate myofibrils.
Ca2+ movement
Depolarisation activates dihydropyridine (DHP) receptor, activating Ca2+ release channel (ryanodine) in sarcoplasmic reticulum membrane. Repolarisation closes the Ca2+ channels, and Ca2+ is pumped back into the SR and bound to calsequestrin.
Types of muscle contraction
Twitch–> single contraction (5Hz)
Sustained contraction–> faster rate of firing (40Hz)
Fate of acetylcholine
Acetylcholine binds to nAChR for ~1ms, then is released into the synaptic cleft and hydrolysed by the enzyme acetylcholinesterase (AChE). The products of this breakdown are acetyl and choline, the latter of which is recycled after uptake by the presynaptic terminal.
Myesthenia Gravis
An autoimmune disease in which there are reduced numbers of AChRs at the NMJ. Results in muscle weakness during sustained activity. Can be treated by prolonging the signal, using AChE inhibitors/neostigmine.
