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Vol. 288, Issue 1, 379-388, January 1999
Department of Health Sciences, University of Technology, Sydney,
Broadway NSW, Australia (L.C.S., G.M.N); and
Queensland Agricultural
Biotechnology Center, Department of Primary Industries, Gehrmann
Laboratories, University of Queensland, St. Lucia QLD, Australia
(R.J.L)
Pacific ciguatoxin-1 (P-CTX-1), is a highly lipophilic cyclic polyether
molecule originating from the marine dinoflagellate Gambierdiscus toxicus. Its effects were investigated on
sodium channel subtypes present in acutely dissociated rat dorsal root ganglion neurons, using whole-cell patch clamp techniques.
Concentrations of P-CTX-1 ranging from 0.2 to 20 nM had no effect on
the kinetics of tetrodotoxin-sensitive (TTX-S) or
tetrodotoxin-resistant (TTX-R) sodium channel activation and
inactivation, however, a concentration-dependent reduction in peak
current amplitude occurred in both channel types. The main actions of 5 nM P-CTX-1 on TTX-S sodium channels were a 13-mV hyperpolarizing shift
in the voltage dependence of sodium channel activation and a 22-mV
hyperpolarizing shift in steady-state inactivation
(h
). In addition, P-CTX-1 caused a rapid
rise in the membrane leakage current in cells expressing TTX-S sodium channels. This effect was blocked by 200 nM TTX, indicating an action
mediated through TTX-S sodium channels. In contrast, the main action of
P-CTX-1 (5 nM) on TTX-R sodium channels was a significant increase in
the rate of recovery from sodium channel inactivation. These results
indicate that P-CTX-1 acts to modify voltage-gated sodium channels
present in peripheral sensory neurons consistent with its action to
increase nerve excitability. This provides an explanation for the
sensory neurological disturbances associated with ciguatera fish poisoning.
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