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Toxicity Of Botulinum Toxin: A Stoichiometric Model For The Locus Of Its Extraordinary Potency And Persistence At The Neuromuscular Junction.

J. Hanig, C. Lamanna
Published 1979 · Chemistry, Medicine

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Abstract The number of botulinum toxin molecules calculated to reach either a diaphragmatic endplate after a minimum lethal dose or a gastrocnemius endplate after a minimal paralyzing dose is in close agreement with both the number of vesicles released per impulse and the finite number of active sites on the endplate for efflux of acetylcholine-containing vesicles. The close agreement in size between botulinum toxin molecules, synaptic vesicles, and the width of neurotubules supports a model in which botulinum toxin physically blocks efflux of acetylcholine. The stoichiometric attachment of botulinum toxin may occur at the critical moment that vesicles fuse with the presynaptic membrane, thereby exposing a receptor. While attachment may be to a ganglioside or neuraminidase-sensitive site, the chemical nature of the receptor is neither defined nor critical for the validity of the model.
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