Transient Receptor Potential Channels Contribute to Pathological Structural and Functional Remodeling After Myocardial Infarction

Rationale:The cellular and molecular basis for post–myocardial infarction (MI) structural and functional remodeling is not well understood. Objective:Our aim was to determine if Ca2+ influx through transient receptor potential canonical (TRPC) channels contributes to post-MI structural and functional remodeling. Methods and Results:TRPC1/3/4/6 channel mRNA increased after MI in mice and was associated with TRPC-mediated Ca2+ entry. Cardiac myocyte–specific expression of a dominant-negative (loss-of-function) TRPC4 channel increased basal myocyte contractility and reduced hypertrophy and cardiac structural and functional remodeling after MI while increasing survival in mice. We used adenovirus-mediated expression of TRPC3/4/6 channels in cultured adult feline myocytes to define mechanistic aspects of these TRPC-related effects. TRPC3/4/6 overexpression in adult feline myocytes induced calcineurin (Cn)-nuclear factor of activated T-cells (NFAT)–mediated hypertrophic signaling, which was reliant on caveolae ...