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Neurotoxins targetting receptor site 5 of voltage‐dependent sodium channels increase the nodal volume of myelinated axons
Author(s) -
Mattei César,
Dechraoui MarieYasmine,
Molgó Jordi,
Meunier Frédéric A.,
Legrand AnneMarie,
Benoit Evelyne
Publication year - 1999
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19990315)55:6<666::aid-jnr2>3.0.co;2-h
Subject(s) - tetrodotoxin , biophysics , sodium channel , chemistry , axon , marine toxin , membrane potential , osmotic concentration , swelling , node of ranvier , receptor , action potential , nodal , electrophysiology , sodium , microbiology and biotechnology , biology , neuroscience , toxin , anatomy , biochemistry , central nervous system , myelin , materials science , organic chemistry , composite material
The effects of a C 57 type ciguatoxin (CTX‐3C) and two types of brevetoxins (PbTx‐1 and PbTx‐3), known to bind to receptor site 5 of the neuronal voltage‐dependent Na + channel‐protein, were studied on the morphology of living frog myelinated axons using confocal laser scanning microscopy. During the action of CTX‐3C, PbTx‐1, and PbTx‐3 (10–50 nM), a marked swelling of nodes of Ranvier was observed without apparent modification of internodal parts of axons. In all cases, toxin‐induced nodal swelling attained a steady‐state within 75–100 min that was well maintained during an additional 90–115 min. The nodal swelling was reversed by an external hyperosmotic solution containing 100 mM D‐mannitol and could be completely prevented by blocking voltage‐dependent Na + channels with 1 μM tetrodotoxin. It is suggested that CTX‐3C, PbTx‐1, and PbTx‐3 by activating Na + channels cause a continuous Na + entry into axons, increasing internal Na + concentration. Such an increase directly or indirectly disturbs the osmotic equilibrium between intra‐ and extra‐axonal media, resulting in an influx of water, which is responsible for the long‐lasting nodal swelling. Similar results were previously reported with two C 60 type ciguatoxins (CTX‐1B and CTX‐4B). Thus, it is concluded that the four types of toxins targetting receptor site 5 of neuronal voltage‐dependent Na + channels, not only enhance nerve membrane excitability but also, on a long‐term basis, cause a marked increase in the axonal volume. J. Neurosci. Res. 55:666–673, 1999. © 1999 Wiley‐Liss, Inc.