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Science 24 September 1976: Vol. 193. no. 4259, pp. 1256 - 1258 DOI: 10.1126/science.785600
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Articles
Science, Vol 193, Issue 4259, 1256-1258
Copyright © 1976 by American Association for the Advancement of Science
Botulinum toxin: mechanism of presynaptic blockade
I Kao,
DB Drachman,
and
DL Price
The mechanism of action of botulinum toxin was analyzed by the use of calcium ionophores and black widow spider venom. Addition of calcium ionophores to nerve-muscle preparations blocked by botulinum toxin did not increase the frequency of miniature end plate potentials. However, the spider venom elicited a barrage of miniature end plate potentials after blockade by botulinum. Electron micrographs of preparations treated with botulinum toxin and then the spider venom revealed clumping of synaptic vesicles at release sites in the otherwise depleted nerve terminals. These findings indicate that the action of botulinum toxin is not due to deficient storage of acetylcholine in vesicles or blockade of calcium entry into nerve terminals. They suggest that the toxin interferes with the acetylcholine release process itself, possibly by blocking exocytosis at the release sites.
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