Voltage-Gated Sodium Channel Toxins: Poisons, Probes, and Future Promise

Abstract
Neurotoxins have served as invaluable agents for identification, purification, and functional characterization of voltage-gated ion channels. Multiple classes of these toxins, which target voltage-gated Na+ channels via high-affinity binding to distinct but allosterically coupled sites, have been identified. The toxins are chemically diverse, including guanidinium heterocycles, a variety of structurally unrelated alkaloids, and multiple families of nonhomologous polypeptides having either related or distinct functions. This review describes the biochemistry and pharmacology of these agents, and summarizes the structure-function relationships underlying their interaction with molecular targets. In addition, we explore recent advances in the use of these toxins as molecular scaffolding agents, drugs, and insecticides.

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