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Nerve membrane sodium channels as the target site of brevetoxins at neuromuscular junctions.
- Source :
-
British journal of pharmacology [Br J Pharmacol] 1986 Dec; Vol. 89 (4), pp. 731-8. - Publication Year :
- 1986
-
Abstract
- Actions of two structurally related toxins, T-17 and brevetoxin-B, isolated from the red-tide dinoflagellate, Ptychodiscus brevis, were studied on the giant axon of the squid and the neuromuscular junctions of the frog and rat. T-17 toxin caused a large increase in the frequency of miniature endplate potentials at nanomolar concentrations. In one typical case with a frog endplate, the frequency increased from 1.9 s-1 before application of 3.5 nM T-17 to 69.3 s-1 within 5 min after application. In the rat muscle, the mean frequency increased from 1.39 s-1 in control to 11.93 s-1 after application of 23.2 nM T-17. The increase in miniature endplate potential frequency was reversed by the addition of 1 microM tetrodotoxin, and was not observed in a solution containing elevated Mg2+ and reduced Ca2+ concentrations. External or internal application of T-17 toxin (2-5 microM) or brevetoxin-B (10-30 microM) to intact or internally perfused squid axons caused a depolarization of the membrane. This depolarization was abolished by the removal of external Na+ or by addition of tetrodotoxin to the external solution. In voltage clamped squid giant axons, exposure to T-17 toxin or brevetoxin-B increased the non-inactivating component of the tetrodotoxin-sensitive sodium current. The sodium current was activated at potentials 15 to 40 mV more negative than control. It is proposed that these toxins modify a fraction of the sodium channels to a form which opens at potentials more negative than normal and which inactivates to a lesser extent. This mechanism would predict a depolarization of the nerve membrane at the neuromuscular junction, thus explaining the increased discharge of transmitter.
Details
- Language :
- English
- ISSN :
- 0007-1188
- Volume :
- 89
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- British journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 2434175
- Full Text :
- https://doi.org/10.1111/j.1476-5381.1986.tb11177.x