Immunosuppressive effects of a novel potassium channel toxin Ktx-Sp2 from Scorpiops Pocoki

Abstract

BackgroundThe cDNA Library of venomous animals could provide abundant bioactive peptides coding information and is an important resource for screening bioactive peptides that target and regulate disease-related ion channels. To further explore the potential medicinal usage of the transcriptome database of Scorpiops Pocoki’s venom gland, this research identified the function of a new potassium channel toxin Ktx-Sp2, whose gene was screened from the database by sequence alignment.ResultsThe mature peptide of Ktx-Sp2 was obtained by genetic engineering. Whole-cell patch-clamp experiment showed that Ktx-Sp2 peptide could effectively block three types of exogenous voltage-gated potassium channels—Kv1.1, Kv1.2 and Kv1.3, among which, the blocking activity for Kv1.3 was relatively high, showing selectivity to some extent. Taking Jurkat T cells as the cell model, this study found that Ktx-Sp2 peptide could also effectively block endogenous Kv1.3, significantly reduce the free calcium concentration in Jurkat T cells, inhibit the activation of Jurkat T cells and reduce the release of inflammatory cytokines IL-2, showing a strong immunosuppressant effect.ConclusionsThis study further proves that the transcriptome database of the Scorpiops Pocoki venom gland is an important resource for discovery of novel bioactive polypeptide coding genes. The newly screened Kv1.3 channel blocker Ktx-Sp2 expanded the range of leading compounds for the treatment of autoimmune diseases and promoted the development and application of scorpion toxin peptides in the field of biomedicine.

Mechanisms Underlying the Inhibition of KV1.3 Channel by Scorpion Toxin ImKTX58

“…To identify bioactive peptides from scorpion venom, we constructed a cDNA library of Isometrus maculatus venom gland tissues and randomly selected and sequenced positive clones from the library to analyze the toxin transcriptome (Zhang et al, 2019). One positive clone was selected for further studies because it included a complete gene open reading frame (ORF) which could encode a toxin polypeptide.…”