The antibody targeting the E314 peptide of human Kv1.3 pore region serves as a novel, potent and specific channel blocker.

PloS One
Xiao-Fang YangKun Liu

Abstract

Selective blockade of Kv1.3 channels in effector memory T (T(EM)) cells was validated to ameliorate autoimmune or autoimmune-associated diseases. We generated the antibody directed against one peptide of human Kv1.3 (hKv1.3) extracellular loop as a novel and possible Kv1.3 blocker. One peptide of hKv1.3 extracellular loop E3 containing 14 amino acids (E314) was chosen as an antigenic determinant to generate the E314 antibody. The E314 antibody specifically recognized 63.8KD protein stably expressed in hKv1.3-HEK 293 cell lines, whereas it did not recognize or cross-react to human Kv1.1(hKv1.1), Kv1.2(hKv1.2), Kv1.4(hKv1.4), Kv1.5(hKv1.5), KCa3.1(hKCa3.1), HERG, hKCNQ1/hKCNE1, Nav1.5 and Cav1.2 proteins stably expressed in HEK 293 cell lines or in human atrial or ventricular myocytes by Western blotting analysis and immunostaining detection. By the technique of whole-cell patch clamp, the E314 antibody was shown to have a directly inhibitory effect on hKv1.3 currents expressed in HEK 293 or Jurkat T cells and the inhibition showed a concentration-dependence. However, it exerted no significant difference on hKv1.1, hKv1.2, hKv1.4, hKv1.5, hKCa3.1, HERG, hKCNQ1/hKCNE1, L-type Ca(2+) or voltage-gated Na(+) currents. The present stu...Continue Reading

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Citations

Aug 14, 2013·The Journal of General Physiology·Jon T SackJames S Trimmer
Oct 24, 2015·Journal of Cellular and Molecular Medicine·Dimitry A ChistiakovAlexander N Orekhov
Jan 1, 2014·PloS One·Jennifer H CoxValerie H Odegard
Jun 5, 2013·Proceedings of the National Academy of Sciences of the United States of America·Sanjeev Kumar UpadhyayK George Chandy
Aug 14, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Cheng FanKun Liu
Aug 9, 2017·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Dimitry A ChistiakovAlexander N Orekhov
Feb 18, 2020·Natural Product Reports·Saumya BajajK George Chandy
Jul 10, 2017·Neuropharmacology·Raymond S Norton, K George Chandy

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Methods Mentioned

BETA
enzymelinked immunosorbent assay
electrophoresis

Software Mentioned

clamfit
Clampex
DNAStar
sigmaplot

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