title: Differential effects of five 'classical' scorpion beta-toxins on rNav1.2a and DmNav1 provide clues on species-selectivity.
abstract: In general, scorpion beta-toxins have been well examined. However, few in-depth studies have been devoted to species selectivity and affinity comparisons on the different voltage-activated Na(+) channels since they have become available as cloned channels that can be studied in heterologous expression systems. As a result, their classification is largely historical and dates from early in vivo experiments on mice and cockroach and fly larvae. In this study, we aimed to provide an updated overview of selectivity and affinity of scorpion beta-toxins towards voltage-activated Na(+) channels of vertebrates or invertebrates. As pharmacological tools, we used the classic beta-toxins AaHIT, Css II, Css IV, Css VI and Ts VII and tested them on the neuronal vertebrate voltage-activated Na(+) channel, rNa(v)1.2a. For comparison, its invertebrate counterpart, DmNav1, was also tested. Both these channels were expressed in Xenopus laevis oocytes and the currents measured with the two-electrode voltage-clamp technique. We supplemented this data with several binding displacement studies on rat brain synaptosomes. The results lead us to propose a general classification and a novel nomenclature of scorpion beta-toxins based on pharmacological activity.
authors.affiliation: Laboratory of Toxicology, University of Leuven, O and N 2, Postbus 922, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Bosmans
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Martin-Eauclaire
authors.forename: Jan
authors.initials: J
authors.lastname: Tytgat
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D005260:Female; D019476:Insect Proteins / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008845:Microinjections; D008969:Molecular Sequence Data; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000145:classification / Q000494:pharmacology*; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D012604:Scorpion Venoms / Q000145:classification / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D013045:Species Specificity; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D009626:Terminology as Topic; D014982:Xenopus laevis
chemical_list: C115646:CSS IV toxin; D019476:Insect Proteins; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; C568253:Scn2A protein, rat; C000654500:Scn2a protein, mouse; D012604:Scorpion Venoms; D015222:Sodium Channels; C066386:scorpion toxin Css II; C042143:toxin VII; C065314:scorpion toxin I, Androctonus