G Protein-Dependent and G Protein-Independent Signaling Pathways and Their Impact on Cardiac Function

G protein-coupled receptors signal through a variety of mechanisms that impact cardiac function, including contractility and hypertrophy. G protein-dependent and G protein-independent pathways each have the capacity to initiate numerous intracellular signaling cascades to mediate these effects. G protein-dependent signaling has been studied for decades and great strides continue to be made in defining the intricate pathways and effectors regulated by G proteins and their impact on cardiac function. G protein-independent signaling is a relatively newer concept that is being explored more frequently in the cardiovascular system. Recent studies have begun to reveal how cardiac function may be regulated via G protein-independent signaling, especially with respect to the ever-expanding cohort of beta-arrestin-mediated processes. This review primarily focuses on the impact of both G protein-dependent and beta-arrestin-dependent signaling pathways on cardiac function, highlighting the most recent data that illustrate the comprehensive nature of these mechanisms of G protein-coupled receptor signaling. (Circ Res. 2011;109:217-230.)