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Updated: Apr 26, 2026

Isolation and Functional Characterization of Human Ventricular Cardiomyocytes from Fresh Surgical Samples
Published on: April 21, 2014
Transient receptor potential channels contribute to pathological structural and functional remodeling after
Catherine A Makarewich1,2, Hongyu Zhang1,2, Jennifer Davis3
1Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA.
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 targeting of TRPCs. TRPC3/4/6 expression in adult feline myocytes increased rested state contractions and increased spontaneous sarcoplasmic reticulum Ca2+ sparks mediated by enhanced phosphorylation of the ryanodine receptor. TRPC3/4/6 expression was associated with reduced contractility and response to catecholamines during steady-state pacing, likely because of enhanced sarcoplasmic reticulum Ca2+ leak.
Conclusions:
Ca2+ influx through TRPC channels expressed after MI activates pathological cardiac hypertrophy and reduces contractility reserve. Blocking post-MI TRPC activity improved post-MI cardiac structure and function.
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