Ca2+ release via InsP3Rs enhances RyR recruitment during Ca2+ transients by increasing dyadic [Ca2+] in cardiomyocytes

Excitation-contraction coupling (ECC) relies on temporally synchronized sarcoplasmic reticulum (SR) Ca2+ release via ryanodine receptors (RyRs) at dyadic membrane compartments. Neurohormones, such as endothelin-1 (ET-1), that act G?q-coupled G protein-coupled (GPCRs) modulate dynamics during ECC and induce SR events involving inositol 1,4,5-trisphosphate (InsP3) (InsP3Rs). How the relatively modest InsP3Rs elicits this action is not resolved. Here we investigated whether actions of handling were mediated by a direct influence levels mechanism contributes to effects ET-1. Using dyad-targeted genetically encoded reporter, found InsP3R activation augmented fluxes transients increased sparks. RyRs required for these effects. These data provide first demonstration GPCR/InsP3 support notion influences facilitating recruitment proximal RyRs. We propose neurohormonal modulation cardiac function.