Peptide toxins as tools in ion channel biology

Animal venom contains ion channel-targeting peptide toxins that inflict paralysis or pain. The high specificity and potency of these toxins for their target ion channels provides enticing opportunities for their deployment as tools in channel biology. Mechanistic studies on toxin-mediated ion channel modulation have yielded landmark breakthroughs in our understanding of channel architectures and gating mechanisms. Toxins have been recently repurposed as powerful structural biology probes to obtain structures of ion channels in elusive toxin-stabilized conformations providing unprecedented insights into channel gating. Insightful glimpses of protein–lipid interactions provided by some of these structures have served as blueprints for electrophysiology-based studies aimed at elucidating the functional roles of these interactions. Moreover, toxins appended with fluorophores have been used for clinical, biophysical, and cell biology-based studies. Herein, we summarize the contributions of ion channel-targeting toxins as tools in voltage-gated ion channel and transient receptor potential channel biology.