Advances in molecular genetics of scorpion neurotoxins

Polypeptide neurotoxins derived from scorpion venoms constitute according to their primary structure and mode of action several distinct groups. Most of these toxins recognize ion channels in neuronal tissues in a specific manner that distinguishes between mammals, Insects and crustaceans and are therefore used as neuropharmacological tools in the study of neuronal membrane excitability. Clarification of the molecular basis for their specificity is of major interest in the study of ion channel gating and is of applicative value. This goal can be achieved either by using synthetic in-vitro folded polypeptides designed with amino add substitutions, or via a molecular genetic approach. Such an approach requires the isolation of the corresponding cDNA clones and their functional expression ex-vivo. A combination of chemical, immunochemical and structural studies with a genetic modificational approach seems to provide the most rational basis for this clarification. The cloning of a variety of cDNAs encoding scorpion neurotoxins together with the successful expression systems established recently in Escherichia coli and insect cells, were a major step towards the achievement of this goal.