Expansion
Acetylcholine acts on nicotinic receptors and is broken down by acetylcholinesterase
Expansion
- Action potential reaches the motor nerve terminal
- Calcium entry triggers release of acetylcholine quanta
- Acetylcholine binds nicotinic receptors on the motor end plate
- Sodium influx creates an end plate potential, which is normally far above threshold: the safety margin
- Muscle action potential propagates, triggering excitation-contraction coupling
- Acetylcholinesterase hydrolyses acetylcholine within milliseconds
Disorders map onto the steps:
- Myasthenia gravis: antibodies against the postsynaptic nicotinic receptor. Fatigable weakness that worsens with activity, improves with anticholinesterases
- Lambert-Eaton: antibodies against presynaptic calcium channels. Weakness improves with repeated activity
- Botulism: blocked acetylcholine release, giving descending flaccid paralysis
- Organophosphates: inhibit acetylcholinesterase, causing depolarising blockade
Anaesthetic agents exploit the receptor directly: suxamethonium is a depolarising agonist, while rocuronium and vecuronium are competitive antagonists reversed by neostigmine or sugammadex.