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• W2023739994 abstract "Scorpion β-toxins represent a particular pharmacological group of voltage-gated sodium channel (VGSC) neurotoxins. They typically shift the voltage dependence of activation to more hyperpolarizing potentials and reduce the peak current amplitude by binding to receptor-site 4. Here, we report the purification and functional characterization of the first voltage-gated sodium channel toxins, CeII8 and CeII9, isolated from the scorpion Centruroides elegans (Thorell, 1876), which is responsible for deadly cases of intoxication in Mexico. The soluble venom was fractionated by gel filtration and ion-exchange chromatography, followed by reversed-phase HPLC. The toxins CeII8 and CeII9 were further purified and both their amino acid sequence and molecular weight were determined. Both toxins were electrophysiologically characterized on four mammalian VGSCs (rNav1.2, rNav1.4, hNav1.5 and rNav1.7) expressed heterologously in Xenopus laevis oocytes, using the two-electrode voltage-clamp technique. Although CeII8 has the highest sequence similarity with scorpion α-toxins, inhibiting the inactivation of VGSCs, 300 nM toxin had a clear β-toxin effect and was selective towards Nav1.7, involved in short-term and inflammatory pain. To the best of our knowledge, CeII8 is the first β-toxin active on Nav1.7. CeII9, a typical anti-mammalian β-toxin, selectively modulated Nav1.4 at a concentration of 700 nM and was, in contrast to CeII8, found to be lethal to mice. Interestingly, both toxins, despite their differences in amino acid sequence, only altered the biophysical properties of a fraction of the expressed sodium channels. Since these effects have also been reported for the β-toxin CssIV, the bioactive surfaces of the toxins have been compared to each other." @default.
• W2023739994 created "2016-06-24" @default.
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• W2023739994 date "2010-09-01" @default.
• W2023739994 modified "2023-10-01" @default.
• W2023739994 title "Isolation and characterization of two novel scorpion toxins: The α-toxin-like CeII8, specific for Nav1.7 channels and the classical anti-mammalian CeII9, specific for Nav1.4 channels" @default.
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• W2023739994 doi "https://doi.org/10.1016/j.toxicon.2010.06.008" @default.
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