An 'Old World' scorpion beta-toxin that recognizes both insect and mammalian sodium channels.
Scorpion toxins that affect sodium channel (NaCh) gating in excitable cells are divided into alpha- and beta-classes. Whereas alpha-toxins have been found in scorpions throughout the world, anti-mammalian beta-toxins have been assigned, thus far, to 'New World' scorpions while anti-insect selective beta-toxins (depressant and excitatory) have been described only in the 'Old World'. This distribution suggested that diversification of beta-toxins into distinct pharmacological groups occurred after the separation of the continents, 150 million years ago. We have characterized a unique toxin, Lqhbeta1, from the 'Old World' scorpion, Leiurus quinquestriatus hebraeus, that resembles in sequence and activity both 'New World'beta-toxins as well as 'Old World' depressant toxins. Lqhbeta1 competes, with apparent high affinity, with anti-insect and anti-mammalian beta-toxins for binding to cockroach and rat brain synaptosomes, respectively. Surprisingly, Lqhbeta1 also competes with an anti-mammalian alpha-toxin on binding to rat brain NaChs. Analysis of Lqhbeta1 effects on rat brain and Drosophila Para NaChs expressed in Xenopus oocytes revealed a shift in the voltage-dependence of activation to more negative membrane potentials and a reduction in sodium peak currents in a manner typifying beta-toxin activity. Moreover, Lqhbeta1 resembles beta-toxins by having a weak effect on cardiac NaChs and a marked effect on rat brain and skeletal muscle NaChs. These multifaceted features suggest that Lqhbeta1 may represent an ancestral beta-toxin group in 'Old World' scorpions that gave rise, after the separation of the continents, to depressant toxins in 'Old World' scorpions and to various beta-toxin subgroups in 'New World' scorpions.
Gordon
Dalia
D
Department of Plant Sciences, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Israel. dgordon@post.tau.ac.il
Ilan
Nitza
N
Zilberberg
Noam
N
Gilles
Nicolas
N
Urbach
Daniel
D
Cohen
Lior
L
Karbat
Izhar
I
Froy
Oren
O
Gaathon
Ariel
A
Kallen
Roland G
RG
Benveniste
Morris
M
Gurevitz
Michael
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary; D007313:Insecta; D008322:Mammals; D008969:Molecular Sequence Data; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D012604:Scorpion Venoms / Q000235:genetics* / Q000494:pharmacology*; D012605:Scorpions; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015222:Sodium Channels / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D014981:Xenopus
D018076:DNA, Complementary; D011994:Recombinant Proteins; D012604:Scorpion Venoms; D015222:Sodium Channels