Nodal swelling produced by ciguatoxin-induced selective activation of sodium channels in myelinated nerve fibers

Neuroscience. 1996 Apr;71(4):1121-31. doi: 10.1016/0306-4522(95)00506-4.


Ciguatoxin-1b, the major toxin involved in ciguatera fish poisoning, and D-mannitol were examined on frog nodes of Ranvier using confocal laser scanning microscopy and conventional current- and voltage-clamp techniques. During the action of 10 nM ciguatoxin-1b, an increase in nodal volume was observed as determined by digital image processing and three-dimensional reconstruction of axons. The increase was prevented by blocking Na+ channels with tetrodotoxin. Ciguatoxin-1b (10 nM) induced high frequency action potential discharges up to 70-100 Hz. Analysis of Na+ current revealed that the toxin modified a current fraction which was activated at resting membrane potential and failed to inactivate. Increasing the osmolality of the external solution by about 50% with D-mannitol restored the nodal volume to its control value and suppressed spontaneous action potentials. In addition, D-mannitol affected unmodified and ciguatoxin-1b-treated Na+ currents in a similar manner causing a reduction of maximum conductance, negative shifts of current reversal potential and modification of the voltage-dependence of current activation and inactivation. In conclusion, ciguatoxin-1b induced a tetrodotoxin-sensitive swelling of nodes of Ranvier and selectively affected the Na+ current of myelinated axons. It is proposed that ciguatoxin-1b, by modifying Na+ current, increased intracellular Na+ concentration which caused water influx and nodal swelling. This may explain some of the reported symptoms of ciguatera fish poisoning. D-mannitol, an agent used for ciguatera treatment, was found to reverse the effects of ciguatoxin-1b by reducing Na+ entry and increasing the efflux of water through its osmotic action. It is the first time that osmotic changes produced by the selective activation of ionic channels, i.e. Na+ channels, are reported.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Ciguatoxins / pharmacology*
  • Mannitol / pharmacology
  • Microscopy, Confocal
  • Nerve Fibers, Myelinated / chemistry
  • Nerve Fibers, Myelinated / drug effects
  • Nerve Fibers, Myelinated / physiology
  • Osmolar Concentration
  • Patch-Clamp Techniques
  • Rana esculenta
  • Ranvier's Nodes / chemistry
  • Ranvier's Nodes / drug effects*
  • Ranvier's Nodes / pathology
  • Sciatic Nerve / chemistry
  • Sciatic Nerve / drug effects*
  • Sciatic Nerve / ultrastructure
  • Sodium / metabolism
  • Sodium Channel Agonists*
  • Tetrodotoxin / pharmacology


  • Sodium Channel Agonists
  • Ciguatoxins
  • Mannitol
  • Tetrodotoxin
  • Sodium