The cAMP-dependent protein kinase type I regulates cardiac excitation-contraction coupling

The cAMP-dependent protein kinase (PKA) consists of two regulatory (R) and two catalytic (C) subunits and comprises two subtypes, PKAI and PKAII, defined by the nature of their regulatory subunits, RIα and RIIα respectively. Whereas PKAII is thought to play a key role in β-adrenergic (β-AR) regulation of cardiac contractility, the function of PKAI is unclear. To address this question, we generated mice with cardiomyocyte-specific and conditional invalidation of the RIα subunit of PKA. Tamoxifen injection in 8 weeks-old mice resulted in a > 70% decrease in RIα protein without modification of other PKA subunits, which was associated with ∼2-fold increased basal PKA activity in RIα-KO mice (P   2-fold (P