Characterization of scorpion α‐like toxin group using two new toxins from the scorpion Leiurus quinquestriatus hebraeus

Two novel toxins, Lqh6 and Lqh7, isolated from the venom of the scorpion Leiurus quinquestriatus hebraeus, have in their sequence a molecular signature (8Q/KPE10) associated with a recently defined group of α‐toxins that target Na channels, namely the α‐like toxins [reviewed in Gordon, D., Savarin, P., Gurevitz, M. & Zinn‐Justin, S. (1998) J. Toxicol. Toxin Rev. 17, 131–159]. Lqh6 and Lqh7 are highly toxic to insects and mice, and inhibit the binding of α‐toxins to cockroach neuronal membranes. Although they kill rodents by intracerebroventricular injection, they do not inhibit the binding of antimammal α‐toxins (e.g. Lqh2) to rat brain synaptosomes, not even at high concentrations. Furthermore, in voltage‐clamp experiments, rat brain Na channels IIA (rNav1.2A) expressed in Xenopus oocytes are not affected by Lqh6 nor by Lqh7 below 3 µm. In contrast, muscular Na channels (rNav1.4 and hNav1.5) expressed in the same cells respond to nanomolar concentrations of Lqh6 and Lqh7 by slowing of Na current inactivation and a leftward shift of the peak conductance–voltage curve. The structural and pharmacological properties of the new toxins are compared to those of other scorpion α‐toxins in order to re‐examine the hallmarks previously set for the α‐like toxin group.