Molecular Basis of Paralytic Neurotoxin Action on Voltage-Sensitive Sodium Channels
Annual rept. 15 Sep 1985-14 Sep 1986
WASHINGTON UNIV SEATTLE DEPT OF PHARMACOLOGY
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In years 1 and 2 of this project, progress was made on several objectives The sites and mechanisms of action on the sodium channel were examined and further defined for three new classes of neurotoxins Goniopora toxins, Brevetoxins, and Conotoxins. Monoclonal antibodies with high affinity for the mammalian neuronal sodium channel were developed and methods to screen them for activity at neurotoxin binding sites were established. Site-directed antibodies against defined regions of the amion acid sequence of the sodium channel were prepared and shown to bind at discrete negatively charged subsites on the extracellular surface of the channel that may form part of neurotoxin receptor sites. Keywords Ion transport.