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

  • Ion channels, receptors and transporters
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Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

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 Ca2+ 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 La3+. Thapsigargin enhanced the current, and its effect was suppressed by La3+ and prevented by pipette inclusion of anti-TRPC1 antibody. Endothlin-1 and angiotensin II enhanced the current that could be inhibited by La3+. 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. Ca2+ 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.

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Acknowledgement

This study was supported by a General Research Fund (771712M) from Research Grant Council of Hong Kong, and a grant from Sun Chieh Yeh Heart Foundation of Hong Kong. Zhang YH, Wu HJ, and Che H are supported by a postgraduate scholarship from University of Hong Kong.

Conflict of interest

None declared.

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Authors and Affiliations

  1. Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China

    Yan-Hui Zhang, Hui-Jun Wu, Hui Che, Hai-Ying Sun, Hung-Fat Tse & Gui-Rong Li

  2. Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China

    Lik-Cheung Cheng, Xin Li & Wing-Kuk Au

  3. Department of Physiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China

    Gui-Rong Li

  4. L4-59, Laboratory Block, FMB, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China

    Gui-Rong Li

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  1. Yan-Hui Zhang
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Correspondence to Gui-Rong Li.

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Zhang, YH., Wu, HJ., Che, H. et al. Functional transient receptor potential canonical type 1 channels in human atrial myocytes. Pflugers Arch - Eur J Physiol 465, 1439–1449 (2013). https://doi.org/10.1007/s00424-013-1291-3

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  • DOI: https://doi.org/10.1007/s00424-013-1291-3

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