Abstract
Abstract : In the third year of this project, we have continued to analyze the effects of newly described neurotoxins on voltage-sensitive sodium channels in mammalian neurons, prepared site-directed antisera against several defined segments of the sodium channel, and used these to probe the structure, function, and distribution of neurotoxin receptor sites on sodium channels. Two pharmacologically distinct subtypes of voltage-sensitive sodium channels have been described in mammalian muscle cells. Venom of the marine snail Conus geographus contains polypeptide toxins of novel structure which inhibit skeletal muscle contraction by preferentially blocking muscle sodium channels. Geographutoxin II (GTX II), the most potent of this family of conotoxins, competitively inhibits binding of saxitoxin to neurotoxin receptor site 1 on muscle sodium channels at concentrations similar to those that inhibit sodium channel function.
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