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 myelinated nerve fibres previously poisoned with Caribbean ciguatoxin-1 (C-CTX-1), a new toxin isolated from the pelagic fish Caranx latus inhabiting the Caribbean region. In current-clamped myelinated axons, C-CTX-1 (50-120 nM) caused spontaneous and repetitive action potential discharges after a short delay. In addition, the toxin produced a marked swelling of nodes of Ranvier of myelinated axons that reached a steady state within about 90 min, as revealed by using confocal laser scanning microscopy. The increased excitability 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 that C-CTX-1, by increasing nerve membrane excitability, enhances Na(+) entry into nodes of Ranvier through TTX-sensitive sodium channels, which directly or indirectly disturb the osmotic equilibrium between intra- and extra-axonal media resulting in an influx of water that was responsible for the long-lasting nodal swelling. The fact, that hyperosmolar D-mannitol either reversed or prevented the neurocellular actions of C-CTX-1, is of particular interest since it provides the rational basis for its use to treat the neurological symptoms of ciguatera fish poisoning in the Caribbean area.
Mattei
C
C
Laboratoire de Neurobiologie Cellulaire et Moléculaire, UPR 9040, CNRS, bât. 32, 1 Avenue de la Terrasse, Gif sur Yvette, France.
Molgó
J
J
Marquais
M
M
Vernoux
J
J
Benoit
E
E
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D002462:Cell Membrane / Q000187:drug effects* / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D048429:Cell Size / Q000187:drug effects; D002922:Ciguatoxins / Q000037:antagonists & inhibitors*; D004234:Diuretics, Osmotic / Q000494:pharmacology; D008297:Male; D008353:Mannitol / Q000494:pharmacology* / Q000627:therapeutic use*; D011893:Rana esculenta; D011901:Ranvier's Nodes / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure
D004234:Diuretics, Osmotic; D002922:Ciguatoxins; D008353:Mannitol