Abstract
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 alpha-toxins that target Na channels, namely the alpha-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 alpha-toxins to cockroach neuronal membranes. Although they kill rodents by intracerebroventricular injection, they do not inhibit the binding of antimammal alpha-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 micro m. 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 alpha-toxins in order to re-examine the hallmarks previously set for the alpha-like toxin group.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Cockroaches / drug effects
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Female
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Humans
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Ion Transport / drug effects
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Lethal Dose 50
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Mice
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Mice, Inbred C57BL
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Models, Molecular
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Molecular Sequence Data
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Muscle Proteins / drug effects
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Muscle Proteins / genetics
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Muscle, Skeletal / chemistry
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Myocardium / chemistry
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NAV1.2 Voltage-Gated Sodium Channel
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NAV1.5 Voltage-Gated Sodium Channel
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Nerve Tissue Proteins / drug effects
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Nerve Tissue Proteins / genetics
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Neurons / drug effects
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Neurotoxins / chemistry
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Neurotoxins / isolation & purification*
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Neurotoxins / pharmacology
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Neurotoxins / toxicity
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Oocytes / drug effects
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Oocytes / metabolism
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Protein Conformation
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Rats
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Recombinant Fusion Proteins / drug effects
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Scorpion Venoms / chemistry*
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Scorpion Venoms / classification
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Scorpion Venoms / isolation & purification*
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Scorpion Venoms / pharmacology
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Scorpion Venoms / toxicity
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Sequence Alignment
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Sequence Homology, Amino Acid
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Sodium / metabolism
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Sodium Channels / drug effects*
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Sodium Channels / genetics
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Sodium Channels / metabolism
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Species Specificity
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Synaptosomes / drug effects
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Synaptosomes / metabolism
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Xenopus laevis
Substances
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Lqh II toxin
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Lqh III toxin
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Lqh6 toxin, Leiurus quinquestriatus hebraeus
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Lqh7 toxin, Leiurus quinquestriatus hebraeus
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Muscle Proteins
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NAV1.2 Voltage-Gated Sodium Channel
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NAV1.5 Voltage-Gated Sodium Channel
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Nerve Tissue Proteins
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Neurotoxins
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Recombinant Fusion Proteins
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SCN2A protein, human
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SCN5A protein, human
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Scn2A protein, rat
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Scn2a protein, mouse
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Scn4a protein, rat
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Scn5a protein, mouse
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Scn5a protein, rat
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Scorpion Venoms
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Sodium Channels
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scorpion toxin receptor
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Sodium