Analysis of Caribbean ciguatoxin-1 effects on frog myelinated axons and the neuromuscular junction

Mattei, Cesar, Marquais, Michel, Schlumberger, Sebastien, Molgo, Jordi, Vernoux, Jean-Paul, Lewis, Richard J. and Benoit, Evelyne (2010) Analysis of Caribbean ciguatoxin-1 effects on frog myelinated axons and the neuromuscular junction. Toxicon, 56 5: 759-767. doi:10.1016/j.toxicon.2009.07.026

Author Mattei, Cesar
Marquais, Michel
Schlumberger, Sebastien
Molgo, Jordi
Vernoux, Jean-Paul
Lewis, Richard J.
Benoit, Evelyne
Title Analysis of Caribbean ciguatoxin-1 effects on frog myelinated axons and the neuromuscular junction
Journal name Toxicon   Check publisher's open access policy
ISSN 0041-0101
Publication date 2010-10
Year available 2009
Sub-type Article (original research)
DOI 10.1016/j.toxicon.2009.07.026
Volume 56
Issue 5
Start page 759
End page 767
Total pages 9
Editor Alan L. Harvey
Place of publication Oxford, U.K.
Publisher Elsevier Science
Collection year 2010
Language eng
Subject C1
9201 Clinical Health (Organs, Diseases and Abnormal Conditions)
1115 Pharmacology and Pharmaceutical Sciences
Formatted abstract
Caribbean ciguatoxin-1 (C-CTX-1) induced, after about 1h exposure, muscle membrane depolarisation and repetitive post-synaptic action potentials (APs) in frog neuromuscular preparations. This depolarising effect was also observed in a Ca2+-free medium with a strong enhancement of spontaneous quantal transmitter release, compared with control conditions. The ciguatoxin-induced increase in release could be accelerated when Ca2+ was present in the extracellular medium. C-CTX-1 also enhanced nerve-evoked quantal acetylcholine (ACh) release. At normal neuromuscular junctions loaded with the fluorescent dye FM1-43, C-CTX-1 induced swelling of nerve terminals, an effect that was reversed by hyperosmotic d-mannitol. In myelinated axons, C-CTX-1 increased nodal membrane excitability, inducing spontaneous and repetitive APs. Also, the toxin enlarged the repolarising phase of APs in control and tetraethylammonium-treated axons. Overall, our data suggest that C-CTX-1 affects nerve excitability and neurotransmitter release at nerve terminals. We conclude that C-CTX-1-induced up-regulation of Na+ channels and the inhibition of K+ channels, at low nanomolar concentrations, produce a variety of functional dysfunctions that are in part responsible for the human muscle skeletal symptoms observed in ciguatera. All these dysfunctions seem to result from the subtle balance between ionic currents, intracellular Na+ and Ca2+ concentrations, and engaged second messengers.
© 2009 Elsevier Ltd.
Keyword Caribbean ciguatoxin
Myelinated axons
Neuromuscular junction
Confocal microscopy
Membrane potential
Quantal acetylcholine release
Sodium channels
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 29 July 2009.

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
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Created: Thu, 22 Apr 2010, 14:00:53 EST by Susan Allen on behalf of Institute for Molecular Bioscience