pIn the present study, BmK αIV, a novel modulator of sodium channels, was cloned from venomous glands of the Chinese scorpion (iButhus martensi/i Karsch) and expressed successfully in iEscherichia coli/i. The iBmK/i αiIV/i gene is composed of two exons separated by a 503 bp intron. The mature polypeptide contains 66 amino acids. BmK αIV has potent toxicity in mice and cockroaches. Surface-plasmon-resonance analysis found that BmK αIV could bind to both rat cerebrocortical synaptosomes and cockroach neuronal membranes, and shared similar binding sites on sodium channels with classical AaH II (α-mammal neurotoxin from the scorpion iAndroctonus australis/i Hector), BmK AS (β-like neurotoxin), BmK IT2 (the depressant insect-selective neurotoxin) and BmK abT (transitional neurotoxin), but not with BmK I (α-like neurotoxin). Two-electrode voltage clamp recordings on rNav1.2 channels expressed in iXenopus laevis/i oocytes revealed that BmK αIV increased the peak amplitude and prolonged the inactivation phase of Nasup+/sup currents. The structural and pharmacological properties compared with those of other scorpion α-toxins suggests that BmK αIV represents a novel subgroup or functional hybrid of α-toxins and might be an evolutionary intermediate neurotoxin for α-toxins./p
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