Identification of a new specific Kv1.3 channel blocker, Ctri9577, from the scorpion Chaerilus tricostatus

Peptides
Shujun XieSong Han

Abstract

Scorpion toxins are valuable resources for discovering new ion channel modulators and drug candidates. Potassium channel Kv1.3 is an important pharmacological target of T cell-mediated autoimmune diseases, which are encouraging the screening and design of the specific peptide blockers for Kv1.3 channel. Ctri9577, the first neurotoxin gene of Chaerilidae family was cloned from the venom of the scorpion Chaerilus tricostatus through the constructing its cDNA library. The sequence analysis showed that the mature peptide of Ctri9577 contained 39 amino acid residues including six conserved cysteines, whose low sequence similarity indicated that it was a new member of α-KTx15 subfamily. By using expression and purification technology, the recombinant peptide was obtained. Subsequently, the electrophysiological experiments indicated that the Ctri9577 peptide selectively inhibited Kv1.3 channel current with an IC(50) of 0.49±0.45 nM without effectively blocking potassium channels Kv1.1, Kv1.2, hERG and SK3. All these findings not only enrich the knowledge of toxins from the Chaerilidae family, but also present a novel potential drug candidate targeting Kv1.3 channels for the therapy of autoimmune diseases.

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Citations

Jan 30, 2014·Biochemical and Biophysical Research Communications·Chang XieYingliang Wu
Oct 30, 2016·Neuropharmacology·David M HousleyErnest A Jennings
Feb 6, 2018·Experimental and Therapeutic Medicine·Jiao ChenYuan Zhang
Mar 10, 2016·The Biochemical Journal·Chuangeng ZhangYingliang Wu
May 28, 2019·The Journal of Venomous Animals and Toxins Including Tropical Diseases·Isadora S OliveiraManuela B Pucca

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