POLYPEPTIDE TOXINS FROM THE VENOMS OF OLD-WORLD AND NEW-WORLD SCORPIONS PREFERENTIALLY BLOCK DIFFERENT POTASSIUM CHANNELS

Venoms from five Old World and two New World scorpions were tested for their ability to block various K+ channels in rat brain synaptosomes. A Rb-86 efflux kinetic assay was used to identify three types of K+ c hannels, Ca2+-independent, voltage-gated, inactivating (A-type) and no ninactivating (delayed rectifier) K+ channels and Ca2+-activated K+ ch annels [J. Physiol. (Lond.) 361:419-440, 441-457 (1985)]. The venoms f rom the Old World scorpions all blocked the A-type K+ channel but not the delayed rectifier K+ channel; only venom from the Israeli scorpion , Leiurus quinquestriatus hebraeus (Lqh), blocked the Ca2+-activated K + channel. In contrast, venoms from the two New World scorpions select ively blocked the delayed rectifier K+ channel. Water-soluble componen ts from Lqh venom and the venom from the Brazilian scorpion, Tityus se rrulatus (Ts), were separated by ion exchange high performance liquid chromatography (HPLC). Seven components that blocked synaptosome K+ ch annels were isolated from Lqh venom by ion exchange HPLC. All seven co mponents blocked the A-type K+ channel; the five most potent toxins ha d IC50 values of 18-40 nM. Two of the components from Lqh venom (one i dentified as charybdotoxin and the other denoted as Lq(k4)) also block ed a Ca2+-activated K+ channel (IC50 = 15 and 60 nM for charybdotoxin and Lq(K4), respectively). Five K+ channel-blocking components were is olated from the Ts venom; all five blocked the delayed rectifier chann el selectively, and the two most potent components had IC50 values of 8 and 30 nM. Several of the more potent Lqh and Ts toxins were purifie d to near-homogeneity by reverse phase HPLC. These toxins should be us eful as ligands for K+ channel purification, for elucidation of K+ cha nnel structure, and for studies of K+ channel function.