Disruption of Protein Kinase A Interaction with A-kinase-anchoring Proteins in the Heart in Vivo EFFECTS ON CARDIAC CONTRACTILITY, PROTEIN KINASE A PHOSPHORYLATION, AND TROPONIN I PROTEOLYSIS

摘要: Protein kinase A (PKA)-dependent phosphorylation is regulated by targeting of PKA to its substrate as a result binding regulatory subunit, R, A-kinase-anchoring proteins (AKAPs). We investigated the effects disrupting AKAPs in heart expressing 24-amino acid subunit RII-binding peptide, Ht31, inactive analog, Ht31P, or enhanced green fluorescent protein adenoviral gene transfer into rat hearts vivo. Ht31 expression resulted loss striated staining pattern type II (RII), indicating from sites on endogenous AKAPs. In absence isoproterenol stimulation, Ht31-expressing had decreased +dP/dtmax and -dP/dtmin but no change left ventricular ejection fraction stroke volume end diastolic pressure versus controls. This suggests that cardiac output unchanged despite +dP/dt -dP/dt. There was also difference troponin I (cTnI), phospholamban, ryanodine receptor (RyR2). Upon infusion, did not differ between At higher doses isoproterenol, increased isoproterenol-stimulated occurred context cTnI, RyR2, phospholamban previously showed N-terminal-cleaved cTnI (cTnI-ND) transgenic mice improves function. Increased N-terminal truncation observed cTnI-ND may help compensate for reduced occurs failure.