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

Pflugers Arch. 2013 Oct;465(10):1439-49. doi: 10.1007/s00424-013-1291-3. Epub 2013 May 19.


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(2+) 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(3+). Thapsigargin enhanced the current, and its effect was suppressed by La(3+) and prevented by pipette inclusion of anti-TRPC1 antibody. Endothlin-1 and angiotensin II enhanced the current that could be inhibited by La(3+). 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(2+) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Angiotensin II / pharmacology
  • Calcium Channels / genetics
  • Calcium Channels / metabolism
  • Calcium Signaling
  • Cells, Cultured
  • Endothelin-1 / pharmacology
  • Heart Atria / cytology
  • Heart Atria / metabolism*
  • Humans
  • Lanthanum / pharmacology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / physiology
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • ORAI1 Protein
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Stromal Interaction Molecule 1
  • TRPC Cation Channels / antagonists & inhibitors
  • TRPC Cation Channels / genetics
  • TRPC Cation Channels / metabolism*
  • Thapsigargin / pharmacology


  • Calcium Channels
  • Endothelin-1
  • Membrane Proteins
  • Neoplasm Proteins
  • ORAI1 Protein
  • ORAI1 protein, human
  • RNA, Messenger
  • STIM1 protein, human
  • Stromal Interaction Molecule 1
  • TRPC Cation Channels
  • transient receptor potential cation channel, subfamily C, member 1
  • Angiotensin II
  • Thapsigargin
  • Lanthanum