Acetylcholine synthesis, vesicular storage, release, and toxin effects
THE CONTEXT
Cholinergic nerve terminals take up choline, synthesize and store acetylcholine, and release it in vesicular quanta. Specific inhibitors and toxins interrupt different steps.
Synthesis and vesicular storage
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Choline is actively taken up across the axonal membrane and acetylated by choline acetyltransferase in the axoplasm, with the help of ATP and coenzyme A.
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Choline uptake is the rate-limiting step in acetylcholine synthesis. Hemicholinium blocks this step and depletes acetylcholine.
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Most acetylcholine is stored in small clear synaptic vesicles aligned mainly near the synaptic membrane.
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A vesicle-associated transporter actively transports acetylcholine into synaptic vesicles. Vesamicol blocks this transporter.
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Large dense-core vesicles lie relatively farther from the synaptic membrane and contain peptide cotransmitters such as VIP.
Quantal release and toxin actions
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Acetylcholine is released in small quanta: the contents of individual vesicles are extruded in pulses by exocytosis.
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A nerve action potential produces synchronous release of multiple quanta, triggering postjunctional events.
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Botulinum toxin inhibits acetylcholine release, whereas black widow spider toxin induces massive release and depletion.
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Botulinum toxins A and B are potent exotoxins responsible for botulism, described as a type of food poisoning.
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These toxins cause prolonged loss of cholinergic transmission by interacting with axonal proteins involved in exocytotic acetylcholine release.
Local therapeutic use of botulinum toxin
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Local injection of minute quantities of botulinum toxin A or its haemagglutinin complex can treat conditions associated with cholinergic nerve overactivity.
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Listed applications include blepharospasm, spastic cerebral palsy, strabismus, spasmodic torticollis, nystagmus, hemifacial spasm, post-stroke spasticity, spasmodic dysphonia, and axillary hyperhidrosis.
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It is also used to remove age-related facial wrinkles.
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Incorrect injection or overdose can be dangerous; listed adverse effects include ptosis, diplopia, facial swelling, and dry mouth.