title: ImKTx1, a new Kv1.3 channel blocker with a unique primary structure.
abstract: Toxins from the venoms of scorpion, snake, and spider are valuable tools to probe the structure-function relationship of ion channels. In this investigation, a new toxin gene encoding the peptide ImKTx1 was isolated from the venom gland of the scorpion Isometrus maculates by constructing cDNA library method, and the recombinant ImKTx1 peptide was characterized physiologically. The mature peptide of ImKTx1 has 39 amino acid residues including six cross-linked cysteines. The electrophysiological experiments showed that the recombinant ImKTx1 peptide had a pharmacological profile where it inhibited Kv1.3 channel currents with IC(50) of 1.70 n± 1.35 µM, whereas 10 µM rImKTx1 peptide inhibited about 40% Kv1.1 and 42% Kv1.2 channel currents, respectively. In addition, 10 µM rImKTx1 had no effect on the Nav1.2 and Nav1.4 channel currents. Multiple sequence alignments showed that ImKTx1 had no homologous toxin peptide, but it was similar with Ca(2+) channel toxins from scorpion and spider in the arrangement of cysteine residues. These results indicate that ImKTx1 is a new Kv1.3 channel blocker with a unique primary structure. Our results indicate the diversity of K(+) channel toxins from scorpion venoms and also provide a new molecular template targeting Kv1.3 channel.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, People's Republic of China.
authors.forename: Zongyun
authors.initials: Z
authors.lastname: Chen
authors.forename: Youtian
authors.initials: Y
authors.lastname: Hu
authors.forename: Song
authors.initials: S
authors.lastname: Han
authors.forename: Shijin
authors.initials: S
authors.lastname: Yin
authors.forename: Yawen
authors.initials: Y
authors.lastname: He
authors.forename: Yingliang
authors.initials: Y
authors.lastname: Wu
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Cao
authors.forename: Wenxin
authors.initials: W
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D057809:HEK293 Cells; D006801:Humans; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D012604:Scorpion Venoms / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D012605:Scorpions / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: C569136:ImKTx1 peptide, Isometrus maculates; D051664:Kv1.3 Potassium Channel; D010455:Peptides; D012604:Scorpion Venoms