TRPC3 and TRPC6 are essential for angiotensin II-induced cardiac hypertrophy

EMBO J. 2006 Nov 15;25(22):5305-16. doi: 10.1038/sj.emboj.7601417. Epub 2006 Nov 2.


Angiotensin (Ang) II participates in the pathogenesis of heart failure through induction of cardiac hypertrophy. Ang II-induced hypertrophic growth of cardiomyocytes is mediated by nuclear factor of activated T cells (NFAT), a Ca(2+)-responsive transcriptional factor. It is believed that phospholipase C (PLC)-mediated production of inositol-1,4,5-trisphosphate (IP(3)) is responsible for Ca(2+) increase that is necessary for NFAT activation. However, we demonstrate that PLC-mediated production of diacylglycerol (DAG) but not IP(3) is essential for Ang II-induced NFAT activation in rat cardiac myocytes. NFAT activation and hypertrophic responses by Ang II stimulation required the enhanced frequency of Ca(2+) oscillation triggered by membrane depolarization through activation of DAG-sensitive TRPC channels, which leads to activation of L-type Ca(2+) channel. Patch clamp recordings from single myocytes revealed that Ang II activated DAG-sensitive TRPC-like currents. Among DAG-activating TRPC channels (TRPC3, TRPC6, and TRPC7), the activities of TRPC3 and TRPC6 channels correlated with Ang II-induced NFAT activation and hypertrophic responses. These data suggest that DAG-induced Ca(2+) signaling pathway through TRPC3 and TRPC6 is essential for Ang II-induced NFAT activation and cardiac hypertrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / physiology*
  • Animals
  • Animals, Newborn
  • Calcium Channels, L-Type / physiology
  • Calcium Signaling
  • Cardiomegaly / metabolism
  • Cardiomegaly / pathology*
  • Cells, Cultured
  • Diglycerides / metabolism
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Ion Channel Gating
  • Membrane Potentials
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology*
  • NFATC Transcription Factors / metabolism
  • Rats
  • Signal Transduction
  • TRPC Cation Channels / physiology*
  • Type C Phospholipases / metabolism
  • Vasoconstrictor Agents / pharmacology*


  • Calcium Channels, L-Type
  • Diglycerides
  • NFATC Transcription Factors
  • TRPC Cation Channels
  • TRPC3 cation channel
  • Trpc6 protein, rat
  • Vasoconstrictor Agents
  • Angiotensin II
  • Inositol 1,4,5-Trisphosphate
  • Type C Phospholipases