Hyperosmolar D-mannitol reverses the increased membrane excitability and the nodal swelling caused by Caribbean ciguatoxin-1 in single frog myelinated axons

The effects of hyperosmolar D-mannitol were studied on single frog myelinat ed nerve fibres previously poisoned with Caribbean ciguatoxin-1 (C-CTX-1), a new toxin isolated from the pelagic fish Caranx latus inhabiting the Cari bbean region. In current-clamped myelinated axons, C-CTX-1 (50-120 nM) caus ed spontaneous and repetitive action potential discharges after a short del ay. In addition, the toxin produced a marked swelling of nodes of Ranvier o f myelinated axons that reached a steady state within about 90 min, as reve aled by using confocal laser scanning microscopy. The increased excitabilit y and the nodal swelling caused by C-CTX-1 were prevented or reversed by an external hyperosmotic solution containing 100 mM D-mannitol. Moreover, the C-CTX-1-induced nodal swelling was completely prevented by the blockade of voltage-sensitive sodium channels by tetrodotoxin (TTX). It is suggested t hat C-CTX-1, by increasing nerve membrane excitability, enhances Naf entry into nodes of Ranvier through TTX-sensitive sodium channels, which directly or indirectly disturb the osmotic equilibrium between intra- and extra-axo nal media resulting in an influx of water that was responsible for the long -lasting nodal swelling. The fact, that hyperosmolar D-mannitol either reve rsed or prevented the neurocellular actions of C-CTX-1, is of particular in terest since it provides the rational basis for its use to treat the neurol ogical symptoms of ciguatera fish poisoning in the Caribbean area. (C) 1999 Elsevier Science B.V. All rights reserved.