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TRPC1 channels are critical for hypertrophic signaling in the heart.

Publication ,  Journal Article
Seth, M; Zhang, Z-S; Mao, L; Graham, V; Burch, J; Stiber, J; Tsiokas, L; Winn, M; Abramowitz, J; Rockman, HA; Birnbaumer, L; Rosenberg, P
Published in: Circ Res
November 6, 2009

RATIONALE: Cardiac muscle adapts to increase workload by altering cardiomyocyte size and function resulting in cardiac hypertrophy. G protein-coupled receptor signaling is known to govern the hypertrophic response through the regulation of ion channel activity and downstream signaling in failing cardiomyocytes. OBJECTIVE: Transient receptor potential canonical (TRPC) channels are G protein-coupled receptor operated channels previously implicated in cardiac hypertrophy. Our objective of this study is to better understand how TRPC channels influence cardiomyocyte calcium signaling. METHODS AND RESULTS: Here, we used whole cell patch clamp of adult cardiomyocytes to show upregulation of a nonselective cation current reminiscent of TRPC channels subjected to pressure overload. This TRPC current corresponds to the increased TRPC channel expression noted in hearts of mice subjected to pressure overload. Importantly, we show that mice lacking TRPC1 channels are missing this putative TRPC current. Moreover, Trpc1(-)(/)(-) mice fail to manifest evidence of maladaptive cardiac hypertrophy and maintain preserved cardiac function when subjected to hemodynamic stress and neurohormonal excess. In addition, we provide a mechanistic basis for the protection conferred to Trpc1(-)(/)(-) mice as mechanosensitive signaling through calcineurin/NFAT, mTOR and Akt is altered in Trpc1(-)(/)(-) mice. CONCLUSIONS: From these studies, we suggest that TRPC1 channels are critical for the adaptation to biomechanical stress and TRPC dysregulation leads to maladaptive cardiac hypertrophy and failure.

Duke Scholars

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Published In

Circ Res

DOI

EISSN

1524-4571

Publication Date

November 6, 2009

Volume

105

Issue

10

Start / End Page

1023 / 1030

Location

United States

Related Subject Headings

  • TRPC Cation Channels
  • TOR Serine-Threonine Kinases
  • Stress, Physiological
  • Proto-Oncogene Proteins c-akt
  • Phosphotransferases (Alcohol Group Acceptor)
  • Myocardium
  • Mice, Knockout
  • Mice
  • Mechanotransduction, Cellular
  • Heart Failure
 

Citation

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MLA
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Seth, M., Zhang, Z. S., Mao, L., Graham, V., Burch, J., Stiber, J., … Rosenberg, P. (2009). TRPC1 channels are critical for hypertrophic signaling in the heart. Circulation Research, 105(10), 1023–1030. https://doi.org/10.1161/CIRCRESAHA.109.206581
Seth, M., Z. S. Zhang, L. Mao, V. Graham, J. Burch, J. Stiber, L. Tsiokas, et al. “TRPC1 channels are critical for hypertrophic signaling in the heart.Circulation Research 105, no. 10 (November 2009): 1023–30. https://doi.org/10.1161/CIRCRESAHA.109.206581.
Seth M, Zhang ZS, Mao L, Graham V, Burch J, Stiber J, et al. TRPC1 channels are critical for hypertrophic signaling in the heart. Circulation research. 2009 Nov;105(10):1023–30.
Seth, M., et al. “TRPC1 channels are critical for hypertrophic signaling in the heart.Circulation Research, vol. 105, no. 10, Nov. 2009, pp. 1023–30. Manual, doi:10.1161/CIRCRESAHA.109.206581.
Seth M, Zhang ZS, Mao L, Graham V, Burch J, Stiber J, Tsiokas L, Winn M, Abramowitz J, Rockman HA, Birnbaumer L, Rosenberg P. TRPC1 channels are critical for hypertrophic signaling in the heart. Circulation research. 2009 Nov;105(10):1023–1030.

Published In

Circ Res

DOI

EISSN

1524-4571

Publication Date

November 6, 2009

Volume

105

Issue

10

Start / End Page

1023 / 1030

Location

United States

Related Subject Headings

  • TRPC Cation Channels
  • TOR Serine-Threonine Kinases
  • Stress, Physiological
  • Proto-Oncogene Proteins c-akt
  • Phosphotransferases (Alcohol Group Acceptor)
  • Myocardium
  • Mice, Knockout
  • Mice
  • Mechanotransduction, Cellular
  • Heart Failure