Historical Perspective of the Characterization of Conotoxins Targeting Voltage-Gated Sodium Channels

Abstract

Marine toxins have potent actions on diverse sodium ion channels regulated by transmembrane voltage (voltage-gated ion channels) or by neurotransmitters (nicotinic acetylcholine receptor channels). Studies of these toxins have focused on varied aspects of venom peptides ranging from evolutionary relationships of predator and prey, biological actions on excitable tissues, potential application as pharmacological intervention in disease therapy, and as part of multiple experimental approaches towards an understanding of the atomistic characterization of ion channel structure. This review examines the historical perspective of the study of conotoxin peptides active on sodium channels gated by transmembrane voltage, which has led to recent advances in ion channel research made possible with the exploitation of the diversity of these marine toxins.

News and views on ion channels in cancer: is cancer a channelopathy?

“…There is a vast and growing canon of animal and plant venom peptide toxins used as pharmacological tools and as potential therapeutics targeting ion channels (for reviews see: Cardoso, 2020 ; Dueñas-Cuellar et al, 2020 ; Groome, 2023 ; Luo et al, 2022 ; Mendes et al, 2023 ; Nogueira Souza et al, 2023 ; Osipov and Utkin, 2023 ; Talukdar et al, 2023 ; Wulff et al, 2019 ). Soricin, one such toxin from the Northern short-tailed shrew ( Blarina brevicauda ), shortened to the C-terminal 13mer peptide (SOR-C13), was shown to be a potent TRPV6 blocker (IC 50 = 14 nM).…”

Voltage-Gated Sodium Channel Inhibition by µ-Conotoxins

“…To date, 27 µ-conotoxins from 15 different species have been functionally characterised to some extent ( Table 1 ), and show distinct selectivity profiles for Na V channels. For recent reviews on µ-conotoxin discovery and selectivity, see [ 16 , 24 , 25 ]. One of the limitations of the clinical utility of µ-conotoxins is their promiscuous and relatively unselective nature [ 17 , 26 ], most likely arising from the high sequence homology across the pore of the various Na V channel subtypes.…”