TRPC1 channels are critical for hypertrophic signaling in the heart.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • 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 Date

  • November 6, 2009

Published In

Volume / Issue

  • 105 / 10

Start / End Page

  • 1023 - 1030

PubMed ID

  • 19797170

Pubmed Central ID

  • PMC2881555

Electronic International Standard Serial Number (EISSN)

  • 1524-4571

Digital Object Identifier (DOI)

  • 10.1161/CIRCRESAHA.109.206581


  • eng

Conference Location

  • United States