The voltage-dependent sodium channel : A well-known molecular target of saxitoxins (cyanotoxins), ciguatoxins and brevetoxins (phycotoxins)

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Английский. Because of its highly selectivity to Na ions, and activation and inactivation gating properties, the voltage-dependent sodium channel plays a fundamental role in generating and conducting action potentials. The channel -subunit is a transmembrane protein composed of 4 domains (DI-DIV), each of them consisting in 6 segments (S1-S6). The segment S4 is responsible for the channel activation and the P loop, connecting S5 and S6, is involved in the channel selectivity. Receptor-sites for toxins have been identified on this -subunit. Indeed, aquatic neurotoxins interacting specifically with this channel are widely distributed among the various organisms responsible for intoxications or envenomations. In particular, saxitoxins, gonyautoxins and derivates, a family of divalent and tricyclic cations produced by some dinoflagellates and cyanobacteria and responsible for Paralytic Shellfish Poisoning, interact with the receptor-site 1 of sodium channels, leading to pore blockade and thus to current and action potential inhibition. This is exemplified by an electrophysiological study of oyster cerebro-visceral nerve sensitivity to saxitoxin which decreases during recent exposure of bivalve mollusks to contaminated dinoflagellates in natural and, in a more subtle way, experimental environments, providing better understanding of the mechanisms associated with the contamination of bivalve mollusks and, therefore, of the means of detecting and counterbalancing this contamination [1]. Ciguatoxins and brevetoxins, two families of cyclic polyethers produced by some dinoflagellates and responsible for Ciguatera Fish Poisoning and Neurologic Shellfish Poisoning, respectively, interact with the receptor-site 5 of sodium channels, leading to partly blockade of inactivation and thus to spontaneous and/or repetitive action potentials. Consequently, toxin-induced cell swelling occurs. This is exemplified by electrophysiological and confocal-imaging studies of toxin effects on vertebrate myelinated nerve fibers [2,3].