title: Isolation and characterization of TsTX-V, a new neurotoxin from Tityus serrulatus scorpion venom which delays the inactivation of Na+ channels.
abstract: TsTX-V, a new neurotoxin from Tityus serrulatus scorpion venom able to induce a prolongation of the inactivation of Na+ channels, has been purified to homogeneity. The venom was chromatographed on CM-cellulose-52 and 13 fractions were first collected. A subsequent stepwise elution chromatography of fraction XI afforded, among other toxins, highly purified TsTX-V, which showed a single band by PAGE, SDS-PAGE or isoelectric focusing, a distinctive amino acid composition, mol. wt. = 7230, pI = 8.0 and i.v. LD50 = 94 +/- 7 micrograms/kg in mice. TsTX-V induced a long lasting hypertension in anesthetized rats and prolonged the action potential of the B fibers of the rabbit vagus nerve at 0.03 microgram/ml. At 0.3 microgram/ml and higher concentrations it caused also a nerve depolarization. These effects on nerve membranes were irreversible and could be suppressed by tetrodotoxin (200-500 nM). Nerve fibers depolarized by high extracellular K+(15-30mM) concentrations still displayed long duration action potentials after TsTX-V treatment. It is suggested that TsTX-V blocks the Na+ channel inactivation system probably as an alpha-toxin.
authors.affiliation: Departamento de Física e Química, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: E C
authors.initials: EC
authors.lastname: Arantes
authors.forename: F
authors.initials: F
authors.lastname: Riccioppo Neto
authors.forename: S V
authors.initials: SV
authors.lastname: Sampaio
authors.forename: C A
authors.initials: CA
authors.lastname: Vieira
authors.forename: J R
authors.initials: JR
authors.lastname: Giglio
mesh_terms: D000200:Action Potentials; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D007928:Lethal Dose 50; D051379:Mice; D008970:Molecular Weight; D009498:Neurotoxins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D012604:Scorpion Venoms / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects*; D014630:Vagus Nerve / Q000187:drug effects
chemical_list: D000596:Amino Acids; D009498:Neurotoxins; D012604:Scorpion Venoms; D015222:Sodium Channels