Scorpion toxin peptide action at the ion channel subunit level

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This review categorizes functionally validated actions of defined scorpion toxin (SCTX) neuropeptides across ion channel subclasses, highlighting key trends in this rapidly evolving field. Scorpion envenomation is a common event in many tropical and subtropical countries, with neuropharmacological actions, particularly autonomic nervous system modulation, causing significant mortality. The primary active agents within scorpion venoms are a diverse group of small neuropeptides that elicit specific potent actions across a wide range of ion channel classes. The identification and functional characterisation of these SCTX peptides has tremendous potential for development of novel pharmaceuticals that advance knowledge of ion channels and establish lead compounds for treatment of excitable tissue disorders. This review delineates the unique specificities of 320 individual SCTX peptides that collectively act on 41 ion channel subclasses. Thus the SCTX research field has significant translational implications for pathophysiology spanning neurotransmission, neurohumoral signalling, sensori-motor systems and excitation-contraction coupling.This article is part of the Special Issue entitled ‘Venom-derived Peptides as Pharmacological Tools.’HIGHLIGHTSSystematic review of scorpion toxin peptides on ion channels (1985 – 2016).Action of scorpion toxin peptides on voltage-gated sodium channels, Kv1 and Kv4-type voltage-gated potassium channels.Action of scorpion toxin peptides on ERG, Kv7, and Kir-type voltage-gated potassium channels.Action of scorpion toxin peptides on calcium-activated potassium channels.Action of scorpion toxin peptides on Cav3 and RYR calcium channels and CFTR and CIC chloride channels.

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