Botulinum neurotoxin and dendrotoxin as probes for studies on transmitter release

J. O. Dolly, J. V. Halliwell, J. D. Black, R. S. Williams, A. Pelchen-Matthews, A. L. Breeze, F. Mehraban, I. B. Othman

Research output: Contribution to journalArticle

98 Scopus citations

Abstract

Acceptors for BoNT have been detected autoradiographically on the terminal membrane of motor nerves at a density of ~ 150/μm2 and shown to mediate toxin internalization, a process deemed essential for its inhibition of transmitter release. DTX, a protein with pronounced central neurotoxicity, was shown to induce convulsive states in hippocampal slices from guinea-pig. Synaptic transmission was facilitated and spontaneous epileptiform activity produced in intact cell populations. Voltage clamp analysis of hippocampal neurones revealed that DTX specifically attenuated a transient voltage-dependent K+ conductance (A-current) and this could account for the excitatory effects observed. Proteinaceous acceptors with high affinity for DTX were identified on brain synaptosomal membranes and found to contain a 65,000 M(r) polypeptide. Their location in rat brain regions was established and contrasted with that of the binding sites for β-bungarotoxin. These findings indicate the usefulness of DTX as a probe for a protein associated with one variety of K+ channel while the larger subunit of BoNT was found to interact with a membraneous component that resides at cholinergic nerve terminals and, hence, is likely to have a unique role.

Original languageEnglish (US)
Pages (from-to)280-303
Number of pages24
JournalJournal de Physiologie
Volume79
Issue number4
StatePublished - 1984

ASJC Scopus subject areas

  • Physiology

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    Dolly, J. O., Halliwell, J. V., Black, J. D., Williams, R. S., Pelchen-Matthews, A., Breeze, A. L., Mehraban, F., & Othman, I. B. (1984). Botulinum neurotoxin and dendrotoxin as probes for studies on transmitter release. Journal de Physiologie, 79(4), 280-303.