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Nerve membrane sodium channels as the target site of brevetoxins at neuromuscular junctions
Author(s) -
Atchison William D.,
Luke Virginia Scruggs,
Narahashi Toshio,
Vogel Stephen M.
Publication year - 1986
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1986.tb11177.x
Subject(s) - tetrodotoxin , depolarization , biophysics , sodium channel , squid , axon , sodium , membrane potential , neuromuscular junction , neurotoxin , marine toxin , toxin , grenouille , biology , chemistry , anatomy , biochemistry , neuroscience , salientia , ecology , organic chemistry , xenopus , gene
1 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. 2 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. 3 The increase in miniature endplate potential frequency was reversed by the addition of 1 μM tetrodotoxin, and was not observed in a solution containing elevated Mg 2+ and reduced Ca 2+ concentrations. 4 External or internal application of T‐17 toxin (2–5 μM) or brevetoxin‐B (10–30 μM) 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. 5 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. 6 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.