1. TRPC3 and TRPC6 are essential for angiotensin II-induced cardiac hypertrophy.
- Author
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Onohara, Naoya, Nishida, Motohiro, Inoue, Ryuji, Kobayashi, Hiroyuki, Sumimoto, Hideki, Sato, Yoji, Mori, Yasuo, Nagao, Taku, and Kurose, Hitoshi
- Subjects
ANGIOTENSINS ,HEART failure ,CARDIAC hypertrophy ,HEART cells ,T cells ,PHOSPHOLIPASES - Abstract
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 (IP3 ) is responsible for Ca2+ increase that is necessary for NFAT activation. However, we demonstrate that PLC-mediated production of diacylglycerol (DAG) but not IP3 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 Ca2+ oscillation triggered by membrane depolarization through activation of DAG-sensitive TRPC channels, which leads to activation of L-type Ca2+ 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 Ca2+ signaling pathway through TRPC3 and TRPC6 is essential for Ang II-induced NFAT activation and cardiac hypertrophy. [ABSTRACT FROM AUTHOR]- Published
- 2006
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