ISOLATION AND CHARACTERIZATION OF TSTX-V, A NEW NEUROTOXIN FROM TITYUS-SERRULATUS SCORPION-VENOM WHICH DELAYS THE INACTIVATION OF NA(+) CHANNELS

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-PACE or isoelectric focusing, a distinctive amino acid composition, mol. wt. = 7230, pI = 8.0 and i.v. LD(50) = 94 +/- 7 mu g/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 mu g/ml. At 0.3 mu g/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.