Neuromuscular junction physiology and electrodiagnostic testing (repetitive nerve stimulation)
Core concept
- Normal transmission and the safety factor
- Action potential -> presynaptic voltage-gated calcium channels (P/Q-type) open -> Ca influx
- -> SNARE-mediated vesicle fusion -> ACh released in quanta
- -> postsynaptic nicotinic AChR on the junctional folds -> end-plate potential (EPP)
- The EPP normally exceeds threshold by a wide margin = the "safety factor" - which is why a normal NMJ never fatigues
- ACh hydrolysed by acetylcholinesterase; MuSK/LRP4/agrin/rapsyn cluster the receptors
- Disease reduces the safety factor, in one of two places
- Postsynaptic (fewer receptors) - myasthenia gravis
- Presynaptic (less release) - Lambert-Eaton, botulism, hypermagnesaemia, aminoglycosides
3 more sections, plus exam facts
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