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Title

Functional transient receptor potential canonical type 1 channels in human atrial myocytes.

Authors

Zhang, Yan-Hui; Wu, Hui-Jun; Che, Hui; Sun, Hai-Ying; Cheng, Lik-Cheung; Li, Xin; Au, Wing-Kuk; Tse, Hung-Fat; Li, Gui-Rong

Abstract

Transient receptor potential (TRP) channels are not well understood in human atrium, and the present study was therefore designed to investigate whether TRPC channels would mediate the nonselective cation current reported previously and are involved in the formation of store-operated Ca entry (SOCE) channels in human atrial myocytes using approaches of whole-cell patch voltage-clamp, RT-PCR, Western blotting, co-immunoprecipitation, and confocal scanning approaches, etc. We found that a nonselective cation current was recorded under K-free conditions in human atrial myocytes, and the current was inhibited by the TRP channel blocker La. Thapsigargin enhanced the current, and its effect was suppressed by La and prevented by pipette inclusion of anti-TRPC1 antibody. Endothlin-1 and angiotensin II enhanced the current that could be inhibited by La. Gene and protein expression of TRPC1 channels were abundant in human atria. In addition, mRNA and protein of STIM1 and Orai1, components of SOCE channels, were abundantly expressed in human atria. Co-immunoprecipitation analysis demonstrated an interaction of TRPC1 with STIM1 and/or Orai1. Ca signaling mediated by SOCE channels was detected by a confocal microscopy technique. These results demonstrate the novel evidence that TRPC1 channels not only mediate the nonselective cation current, but also form SOCE channels in human atria as a component. TRPC1 channels can be activated by endothelin-1 or angiotensin II, which may be involved in the atrial electrical remodeling in patients with atrial fibrillation.

Subjects

TRP channels; MUSCLE cells; POLYMERASE chain reaction; IMMUNOPRECIPITATION; CALCIUM channels; CELLULAR signal transduction; WESTERN immunoblotting

Publication

Pflügers Archiv: European Journal of Physiology, 2013, Vol 465, Issue 10, p1439

ISSN

0031-6768

Publication type

Academic Journal

DOI

10.1007/s00424-013-1291-3

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