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

Naoya Onohara, Motohiro Nishida, Ryuji Inoue, Hiroyuki Kobayashi, Hideki Sumimoto, Yoji Sato, Yasuo Mori, Taku Nagao, Hitoshi Kurose

Research output: Contribution to journalArticle

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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 Ca2+-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.

Original languageEnglish
Pages (from-to)5305-5316
Number of pages12
JournalEMBO Journal
Volume25
Issue number22
DOIs
Publication statusPublished - Nov 15 2006

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NFATC Transcription Factors
Cardiomegaly
Angiotensin II
Diglycerides
Chemical activation
Type C Phospholipases
Cardiac Myocytes
Inositol 1,4,5-Trisphosphate
Depolarization
Clamping devices
Muscle Cells
Rats
Heart Failure
Membranes
Growth

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

TRPC3 and TRPC6 are essential for angiotensin II-induced cardiac hypertrophy. / Onohara, Naoya; Nishida, Motohiro; Inoue, Ryuji; Kobayashi, Hiroyuki; Sumimoto, Hideki; Sato, Yoji; Mori, Yasuo; Nagao, Taku; Kurose, Hitoshi.

In: EMBO Journal, Vol. 25, No. 22, 15.11.2006, p. 5305-5316.

Research output: Contribution to journalArticle

Onohara, Naoya ; Nishida, Motohiro ; Inoue, Ryuji ; Kobayashi, Hiroyuki ; Sumimoto, Hideki ; Sato, Yoji ; Mori, Yasuo ; Nagao, Taku ; Kurose, Hitoshi. / TRPC3 and TRPC6 are essential for angiotensin II-induced cardiac hypertrophy. In: EMBO Journal. 2006 ; Vol. 25, No. 22. pp. 5305-5316.
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