Essential role of TRPC1 channels in cardiomyoblasts hypertrophy mediated by 5-HT2A serotonin receptors

Biochem Biophys Res Commun. 2010 Jan 1;391(1):979-83. doi: 10.1016/j.bbrc.2009.12.001. Epub 2009 Dec 11.

Abstract

Serotonin (5-HT) participates in the development of cardiac hypertrophy through 5-HT(2A) serotonin receptors. The hypertrophic growth of cardiomyoblasts induced by 5-HT(2A) receptors involves the activation of the Ca(2+) responsive calcineurin/NFAT pathway. However, the mechanism whereby NFAT is activated by 5-HT(2A) receptors remains indeterminate. In this study, we examined whether transient receptor potential canonical (TRPC) channels participate in NFAT activation and hypertrophic response triggered by 5-HT. We demonstrate that TRPC1 expression is upregulated in 5-HT-treated rat cardiomyoblasts whereas TRPC6 is induced in a mouse model of heart hypertrophy. Moreover, TRPC1 knockdown by small interfering RNA inhibits NFAT activation and hypertrophic response mediated by 5-HT(2A) receptors. These findings provide new insights about a mechanistic basis for the activation of the calcineurin/NFAT pathway by 5-HT(2A) receptors and highlight the critical role of TRPC1 in the development of cardiac hypertrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiomegaly / genetics
  • Cardiomegaly / metabolism*
  • Cardiomegaly / pathology
  • Cell Line
  • Disease Models, Animal
  • Gene Knockdown Techniques
  • Male
  • Mice
  • Mice, Inbred Strains
  • Myoblasts, Cardiac / drug effects
  • Myoblasts, Cardiac / metabolism*
  • Myoblasts, Cardiac / pathology
  • NFATC Transcription Factors / metabolism
  • RNA, Small Interfering / genetics
  • Rats
  • Receptor, Serotonin, 5-HT2A / metabolism*
  • Serotonin / pharmacology
  • Serotonin 5-HT2 Receptor Agonists
  • TRPC Cation Channels / genetics
  • TRPC Cation Channels / metabolism*
  • TRPC6 Cation Channel

Substances

  • NFATC Transcription Factors
  • RNA, Small Interfering
  • Receptor, Serotonin, 5-HT2A
  • Serotonin 5-HT2 Receptor Agonists
  • TRPC Cation Channels
  • TRPC6 Cation Channel
  • Trpc6 protein, mouse
  • transient receptor potential cation channel, subfamily C, member 1
  • Serotonin