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TRPC3 and TRPC6 are essential for angiotensin II‐induced cardiac hypertrophy
Author(s) -
Onohara Naoya,
Nishida Motohiro,
Inoue Ryuji,
Kobayashi Hiroyuki,
Sumimoto Hideki,
Sato Yoji,
Mori Yasuo,
Nagao Taku,
Kurose Hitoshi
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601417
Subject(s) - biology , trpc3 , trpc6 , angiotensin ii , medicine , renin–angiotensin system , muscle hypertrophy , endocrinology , microbiology and biotechnology , biochemistry , receptor , trpc , transient receptor potential channel , blood pressure
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.