Professor David J. Adams, Health Innovations Research Institute, RMIT University, Melbourne, VIC.
Marine cone snails have developed a distinctive repertoire of small, disulphide bonded peptides (conotoxins) as part of highly evolved venoms used for prey capture and defence. These peptides target a wide range of voltage- and ligand-gated ion channels, transporters and receptors with exquisite selectivity making them an invaluable source of ligands for studying the role and properties of these targets in normal and diseased states. A number of these peptides have shown efficacy in vivo as inhibitors of voltage-gated neuronal calcium (Cav) channels and are in preclinical development for the treatment of chronic and neuropathic pain. In this context, I will discuss the discovery and development of a class of analgesic conotoxins that modulate Cav channels in sensory neurons via a G protein-coupled receptor mechanism. Our recent findings identify GABAB receptor-mediated inhibition of Cav2.2 and Cav2.3 as targets in pain pathways for these and novel ‘designer’ conotoxins.