Vm24, a natural immunosuppressive peptide, potently and selectively blocks Kv1.3 potassium channels of human T cells

Zoltan Varga, Georgina Gurrola-Briones, Ferenc Papp, Ricardo C. Rodriguez De La Vega, Gustavo Pedraza-Alva, Rajeev B. Tajhya, Rezso Gaspar, Luis Cardenas, Yvonne Rosenstein, Christine Beeton, Lourival D. Possani, Gyorgy Panyi

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58 Citations (Scopus)

Abstract

Blockade of Kv1.3 K+ channels in T cells is a promising therapeutic approach for the treatment of autoimmune diseases such as multiple sclerosis and type 1 diabetes mellitus. Vm24 (α-KTx 23.1) is a novel 36-residue Kv1.3-specific peptide isolated from the venom of the scorpion Vaejovis mexicanus smithi. Vm24 inhibits Kv1.3 channels of human lymphocytes with high affinity (Kd = 2.9 pM) and exhibits >1500-fold selectivity over other ion channels assayed. It inhibits the proliferation and Ca2+ signaling of human T cells in vitro and reduces delayed-type hypersensitivity reactions in rats in vivo. Our results indicate that Vm24 has exceptional pharmacological properties that make it an excellent candidate for treatment of certain autoimmune diseases.

Original languageEnglish
Pages (from-to)372-382
Number of pages11
JournalMolecular pharmacology
Volume82
Issue number3
DOIs
Publication statusPublished - Sep 2012

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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    Varga, Z., Gurrola-Briones, G., Papp, F., Rodriguez De La Vega, R. C., Pedraza-Alva, G., Tajhya, R. B., Gaspar, R., Cardenas, L., Rosenstein, Y., Beeton, C., Possani, L. D., & Panyi, G. (2012). Vm24, a natural immunosuppressive peptide, potently and selectively blocks Kv1.3 potassium channels of human T cells. Molecular pharmacology, 82(3), 372-382. https://doi.org/10.1124/mol.112.078006