Essential role of TRPC1 channels in cardiomyoblasts hypertrophy mediated by 5-HT2A serotonin receptors.
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.
Vindis
Cécile
C
Department of Vascular Biology, IFR150, CHU Rangueil, INSERM U-858/I2MR, Toulouse, France. cecile.vindis@inserm.fr
D'Angelo
Romina
R
Mucher
Elodie
E
Nègre-Salvayre
Anne
A
Parini
Angelo
A
Mialet-Perez
Jeanne
J
D000818:Animals; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D004195:Disease Models, Animal; D055785:Gene Knockdown Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D032386:Myoblasts, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D050778:NFATC Transcription Factors / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D058826:Serotonin 5-HT2 Receptor Agonists; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*; D000074287:TRPC6 Cation Channel
D050778:NFATC Transcription Factors; D034741:RNA, Small Interfering; D044402:Receptor, Serotonin, 5-HT2A; D058826:Serotonin 5-HT2 Receptor Agonists; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C492146:Trpc6 protein, mouse; C096351:transient receptor potential cation channel, subfamily C, member 1; D012701:Serotonin