TRPC1 Channels Mediate the Nonselective Cation Current and Store-Operated Calcium Channels in Human Atrial Myocytes

Abstract

Little information is available in the literature regarding transient receptor potential (TRP) channels in human atrial myocytes. The present study was designed to investigate whether TRPC channels would mediate the nonselective cation current reported previously and store-operated Ca2+ entry channels (SOCs) in human atrial myocytes using approaches of whole-cell patch voltage-clamp, RT-PCR, Western blot analysis, confocol microscopy, and co-immunoprecipitation. It was found that the nonselective cation current was recorded under K+-free conditions in human atrial myocytes, and the current was inhibited by the nonspecific TRP channel blocker La3+. The TRPC1 channel activator thapsigargin activated the current, and the effect was suppressed by La3+ and prevented by pipette inclusion of anti-TRPC1 antibody. In addition, confocol microscopic experiment revealed intracellular Ca2+ transient mediated by SOCs in human atrial myocytes, which was inhibited or prevented by La3+. The mRNAs and proteins of STIM1 and Orai1 (components of SOCs), were abundantly expressed in human atria. Co-immunoprecipitation analysis demonstrated an interaction of TRPC1 with STIM1 and/or Orai1. Interestingly, protein expression of TRPC1 and STIM1, but not Orai1, was upregulated in human atria with atrial fibrillation. Our results indicate that the novel information that TRPC1 channels not only mediate the nonselective cation current, but also is a component of SOCs in human atria. The upregulation of TRPC1 and STIM1 in human atria with atrial fibrillation may suggest that TRPC1 channels and SOCs are likely involved in the atrial electrical and/or structure remodeling in patients with atrial fibrillation.