Which molecular mechanism underlies the skeletal muscle paralysis produced by botulinum toxin?
- A Cleavage of SNARE proteins required for fusion of acetylcholine vesicles with the presynaptic membrane ✓
- B Competitive blockade of postsynaptic nicotinic receptors at the motor end plate
- C Irreversible inhibition of acetylcholinesterase at the synaptic cleft
- D Blockade of voltage-gated sodium channels in the motor nerve terminal
Correct answer: A. Cleavage of SNARE proteins required for fusion of acetylcholine vesicles with the presynaptic membrane
Explanation
Botulinum toxin is internalised into cholinergic nerve terminals where its light chain cleaves SNARE proteins such as SNAP-25, syntaxin or synaptobrevin. Without these proteins, acetylcholine-containing vesicles cannot fuse with the presynaptic membrane, so transmitter release fails. Postsynaptic nicotinic blockade is the mechanism of curare-like agents, cholinesterase inhibition causes excess acetylcholine rather than paralysis from lack of it, and sodium channel blockade is the action of local anaesthetics and tetrodotoxin.
Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.
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