Differential actions of pacific ciguatoxin-1 on sodium channel subtypes in mammalian sensory neurons
1999
Strachan, Liesl C. | Lewis, Richard J. | Nicholson, Graham M.
Pacific ciguatoxin-1 (P-CTX-1), is a highly lipophilic cyclic polyether molecule originating from the marine dinoflagellateGambierdiscus 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.
Afficher plus [+] Moins [-]Mots clés AGROVOC
Informations bibliographiques
Cette notice bibliographique a été fournie par Queensland Department of Agriculture and Fisheries
Découvrez la collection de ce fournisseur de données dans AGRIS