 The neuromuscular junction (NMJ) is the synapse between the presynaptic motor neurone and the postsynaptic muscle membrane. The axon divides into terminal buttons that invaginate into the muscle fibre. The synaptic cleft is 50-70 nm wide and filled with extracellular fluid. The orifices lie opposite the release points for Ach and contain high concentrations of acetylcholinesterase.
There are 3 types of Ach receptor at the NMJ
1. Postjunctional (neuromuscular transmission)
2. Prejunctional (plays a role in fade phenomenon)
3. Extrajunctional (normally small numbers, seen to proliferate post-burns and in muscle disease)
Electrical transmission through the NMJ
Events in transmission through the NMJ
The action potential conducted along the motor nerve causes depolarisation and an influx of calcium. The influx of calcium stimulates the release of Ach from storage vesicles into the synapse. Ach binds to nicotinic receptors on the motor end plate. Stimulation of the Ach receptor results in opening of sodium channels (and some potassium channels), and influx of sodium and potassium into the cell results in depolarisation. Depolarisation is termed "end plate potential" (EPP). If the EPP is sufficiently large, an action potential is produced, muscle contraction occurs and Ach is metabolised by acetylcholinesterase.
Nicotinic cholinergic receptor
The nicotinic receptor at the NMJ contains 5 subunits, which surround the sodium channel. Ach binds to two of these subunits; (alpha) binding of Ach results in opening of the sodium channel for 1 millisecond.
Methods to alter transmission at the NMJ
 Decrease Ach at NMJ
Inhibit Ach synthesis or release (e.g. hemicholinium blocks the uptake of choline into the nerve terminal, which results in depletion of Ach).
Increase Ach or Ach effect at NMJ
Results in nicotinic effect, and thus depolarisation.
Block nicotinic cholinergic receptors at NMJ by competitive blockade (mechanism of action of most therapeutic NMJ blockers)
ArticleDate:20050126
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