Neurotoxins targetting receptor site 5 of voltage-dependent sodium channels increase the nodal volume of myelinated axons
✍ Scribed by César Mattei; Marie-Yasmine Dechraoui; Jordi Molgó; Frédéric A. Meunier; Anne-Marie Legrand; Evelyne Benoit
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 108 KB
- Volume
- 55
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
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 voltagedependent 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 voltagedependent 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.