Toxins targeting voltage-activated Ca2+ channels and their potential biomedical applications

Voltage-gated Ca(2+) (CaV) channels are transmembrane proteins primarily formed by an ion-conducting α 1 subunit that can associate with auxiliary β and α2δ subunits. Ca(2+) entering the cell through these channels serves as a versatile second messenger of electrical signaling, initiating numerous different cellular processes ranging from gene expression to cell fertilization, neuronal transmission and cell death. CaV channels, as other ion channels, are targets for numerous ligands including naturally occurring peptide toxins. Some of these peptide toxins are invaluable tools for studying their structure and function and have potential therapeutic applications. Here, we present an overview of the current knowledge regarding the structure and function of CaV channels as well as their role in human disease, and highlight some of the growing applications of peptide toxins targeting CaV channels. Analysis and understanding of the molecular strategy used by these peptide toxins might allow the design of novel classes of therapeutic agents acting on specific targets with high selectivity and efficacy.