FUNCTIONAL-ANATOMY OF SCORPION TOXINS AFFECTING SODIUM-CHANNELS

Long chain scorpion toxins (made of 60 to 70 amino acids) acting on vo ltage-gated sodium channels in excitable cells are responsible for hum an envenomation, and comprise alpha-toxins that inhibit sodium current inactivation and beta-toxins, that modify the activation process. The se toxins may be further divided according to their pharmacological ac tivities. Thus, alpha-toxins highly active on mammals or insects, as w ell as alpha-like toxins may be distinguished within the alpha-toxin c lass. The beta-toxin class includes toxins active on mammals and, as a separate group, the excitatory and depressant toxins active exclusive ly on insects. All these toxins possess 4 disulfide bridges and share 15 similar non cystine residues. Accordingly, their 3D structure is hi ghly conserved, comprising an a-helix and a triple stranded beta-sheet . The most solvent exposed turns of this structure are prone to insert ions or deletions, and accordingly correspond to the most structurally variable regions of the toxins. They have been tested by chemical mod ification (on several toxins) and site-directed mutagenesis analysis ( of Lqh alpha IT) for their possible involvement in the interactions wi th sodium channels.