From Foe to Friend: Using Animal Toxins to Investigate Ion Channel Function

Abstract

Ion channels are vital contributors to cellular communication in a wide range of organisms, a distinct feature that renders this ubiquitous family of membrane-spanning proteins a prime target for toxins found in animal venom. For many years, the unique properties of these naturally-occurring molecules have enabled researchers to probe the structural and functional features of ion channels and to define their physiological roles in normal and diseased tissues. To illustrate their considerable impact on the ion channel field, this review will highlight fundamental insights into toxin-channel interactions as well as recently developed toxin screening methods and practical applications of engineered toxins.

MmTX1 and MmTX2 from coral snake venom potently modulate GABA A receptor activity

“…For many years, animal venoms have been a valuable source of toxins for studying the functional properties and pharmacologic sensitivities of receptor and ion channel families (60)(61)(62). However, no animal toxins have been identified that selectively target GABA A receptors at subnanomolar concentrations.…”

Bacterial Voltage-Gated Sodium Channels (BacNaVs) from the Soil, Sea, and Salt Lakes Enlighten Molecular Mechanisms of Electrical Signaling and Pharmacology in the Brain and Heart

“…Diverse organisms in nature target the VSDs of vertebrate Na V s by deploying small protein toxins 193 . These “gating modifying” neurotoxins are classically described to bind to the VSDs of DII or DIV (Fig.…”

Sustained inhibition of the Na V 1.7 sodium channel by engineered dimers of the domain II binding peptide GpTx-1

“…7 The traditional method for investigating structure-activity relationships (SAR) in complex natural peptides is the alanine scan, where each amino acid in the peptide sequence is individually replaced with an Ala residue. 8 As the native side chain is exchanged for a methyl group, amino acids important to the binding interaction with the target protein are identified where the contribution of the substituted residue is lost or weakened.…”