title: Polypeptide toxins from the venoms of Old World and New World scorpions preferentially block different potassium channels.
abstract: 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.
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, Baltimore 21201.
authors.forename: M P
authors.initials: MP
authors.lastname: Blaustein
authors.forename: R S
authors.initials: RS
authors.lastname: Rogowski
authors.forename: M J
authors.initials: MJ
authors.lastname: Schneider
authors.forename: B K
authors.initials: BK
authors.lastname: Krueger
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000502:physiology; D004357:Drug Synergism; D010455:Peptides / Q000302:isolation & purification / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D012413:Rubidium / Q000493:pharmacokinetics; D012414:Rubidium Radioisotopes; D012604:Scorpion Venoms / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014118:Toxins, Biological / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D010455:Peptides; D015221:Potassium Channels; D012414:Rubidium Radioisotopes; D012604:Scorpion Venoms; D014118:Toxins, Biological; D012413:Rubidium; D002118:Calcium