RT Journal Article
SR Electronic
T1 Polypeptide toxins from the venoms of Old World and New World scorpions preferentially block different potassium channels.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 932
OP 942
VO 40
IS 6
A1 M P Blaustein
A1 R S Rogowski
A1 M J Schneider
A1 B K Krueger
YR 1991
UL http://molpharm.aspetjournals.org/content/40/6/932.abstract
AB 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 86Rb efflux kinetic assay was used to identify three types of K+ channels, Ca(2+)-independent, voltage-gated, inactivating (A-type) and noninactivating (delayed rectifier) K+ channels and Ca(2+)-activated K+ channels [J. Physiol. (Lond.) 361:419-440, 441-457 (1985)]. The venoms from 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 quinqestriatus hebraeus (Lqh), blocked the Ca(2+)-activated K+ channel. In contrast, venoms from the two New World scorpions selectively blocked the delayed rectifier K+ channel. Water-soluble components from Lqh venom from the Brazillian scorpion, Tityus serrulatus (Ts), were separated by ion exchange high performance liquid chromatography (HPLC). Seven components that blocked synaptosome K+ channels were isolated from Lqh venom by ion exchange HPLC. All seven components blocked the A-type K+ channel; the five most potent toxins had IC50 values of 18-40 nM. Two of the components from Lqh venom (one identified as charybdotoxin and the other denoted as Lqk4) also blocked a Ca(2+)-activated K+ channel (IC50 = 15 and 60 nM for charybdotoxin and Lqk4, respectively). Five K+ channel-blocking components were isolated from the Ts venom; all five blocked the delayed rectifier channel 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 purified to near-homogeneity by reverse phase HPLC. These toxins should be useful as ligands for K+ channel purification, for elucidation of K+ channel structure, and for studies of K+ channel function.