Compartmentalization of β-adrenergic signals in cardiomyocytes

Abstract

Under β-adrenergic stimulation, the distribution of cAMP is highly restricted at distinct intracellular domains for compartmentalized activation of protein kinase A, which promotes selective phosphorylation of proteins for contractile responses in cardiomyocytes. This is primarily due to a concerted effort between restrictions of cAMP distribution by a family of phosphodiesterases and locally anchored protein kinase A by a family of scaffold A kinase-anchoring proteins. Moreover, these regulatory mechanisms underlie the cross talk between β-adrenergic signals and other receptor-stimulated signaling cascades, which alters the compartmentalized β-adrenergic signals for proper contractility in myocardium. Maintaining integrity of compartmentalized β-adrenergic signals is critical for physiological cardiac function and for preventing development of cardiac diseases.