The pharmacology of voltage-gated sodium channel activators

Abstract

Toxins and venom components that target voltage-gated sodium (Na_V) 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. Na_V 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 Na_V channels and are important tools due to their at times exquisite subtype-selectivity. We review the pharmacology of Na_V 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.'

Keywords: Activator; Pharmacology; Toxin; Voltage sensor; Voltage-gated sodium channel.