Toxins interacting with ether-à-go-go-related gene voltage-dependent potassium channels

The critical role that ether-à-go-go-related gene (erg) K+ channels play in mating in Caenorhabditis elegans, neuronal seizures in Drosophila and cardiac action potential repolarization in humans has been well documented. Three erg genes (erg1, erg2 and erg3) have been identified and characterized. A structurally diverse number of compounds block these channels, but do not display specificity among the different channel isoforms. In this review we describe the blocking properties of several peptides, purified from scorpion, sea anemone and spider venoms, which are selective for certain members of the ERG family of channels. These peptides do not behave as classical pore blockers and appear to modify the gating properties of the channel. Genomic studies predict the existence of many other novel peptides with the potential of being more selective for ERG channels than those discussed here.