Cardiomyocyte PKA Ablation Enhances Basal Contractility While Eliminates Cardiac β-Adrenergic Response Without Adverse Effects on the Heart

Rationale: Protein Kinase A (PKA) is a major mediator of β-adrenergic (βAR) regulation of cardiac function but other mediators have also been suggested. Reduced PKA basal activity and activation are linked to cardiac diseases. However, how complete loss of PKA activity impacts on cardiac physiology and if it causes cardiac dysfunction have never been determined. Objective: We set to determine how the heart adapts to the loss of cardiomyocyte PKA activity and if it elicits cardiac abnormalities.Methods and Results:(1) Cardiac PKA activity was almost completely inhibited by expressing a PKA inhibitor peptide in cardiomyocytes (cPKAi) in mice; (2) cPKAi reduced basal phosphorylation of two myofilament proteins (troponin I, cardiac myosin binding protein C), and one longitudinal SR protein (phospholamban), but not of the sarcolemmal proteins (Cav1.2 α1c, phospholemman), dyadic protein RyR2 and nuclear protein CREB at their PKA phosphorylation sites; (3) cPKAi increased the expression of CaMKII, the Cav1.2 β s...