The pharmacology of voltage-gated sodium channel activators

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Toxins and venom components that target voltage-gated sodium (NaV) channels have evolved numerous times due to the importance of this class of ion channels in the normal physiological function of peripheral and central neurons as well as cardiac and skeletal muscle. NaV channel activators in particular have been isolated from the venom of spiders, wasps, snakes, scorpions, cone snails and sea anemone and are also produced by plants, bacteria and algae. These compounds have provided key insight into the molecular structure, function and pathophysiological roles of NaV channels and are important tools due to their at times exquisite subtype-selectivity. We review the pharmacology of NaV channel activators with particular emphasis on mammalian isoforms and discuss putative applications for these compounds.This article is part of the Special Issue entitled ‘Venom-derived Peptides as Pharmacological Tools.’HIGHLIGHTSVoltage-gated sodium channel activator toxins occur in many venoms.Sodium channel activators are important tool compounds and drug leads.These compounds modulate voltage-gated sodium channels with high selectivity.

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