Chinese-scorpion (Buthus martensi Karsch) toxin BmK αIV, a novel modulator of sodium channels: from genomic organization to functional analysis

• DOI: 10.1042/bj20060035
• Publication Date: 2006-10-14T01:31:38Z
• Authors: Zhi-Fang Chai; Mang-Mang Zhu; Zhan-Tao Bai; Tong Liu; Miao Tan; Xue-Yan Pang; Yong-Hua Ji
• Keywords: Male; Neurons; 0301 basic medicine; Ion Transport; NAV1.2 Voltage-Gated Sodium Channel; Base Sequence; Circular Dichroism; Cell Membrane; Genetic Vectors; Molecular Sequence Data; Neurotoxins; Cockroaches; Nerve Tissue Proteins; 3. Good health; Evolution, Molecular; Lethal Dose 50; Mice; 03 medical and health sciences; Genes; Animals; Female; Amino Acid Sequence; Cloning, Molecular

In the present study, BmK αIV, a novel modulator of sodium channels, was cloned from venomous glands of the Chinese scorpion (Buthus martensi Karsch) and expressed successfully in Escherichia coli. The BmK αIV 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 Androctonus australis 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 Xenopus laevis oocytes revealed that BmK αIV increased the peak amplitude and prolonged the inactivation phase of Na+ 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.