Myocardial activation of the ?-Adrenergic Receptor Kinase (?ARK1) by Protein Kinase C (PKC) in vivo

Body. Chronic stimulation of Gq-coupled receptors in the heart leads to PKC activation and myocyte hypertrophy, a precursor to heart failure. βARK1 is a G-protein-coupled receptor kinase (GRK) which phosphorylates and desensitizes agonist-occupied β-adrenergic receptors (βARs), which are critical for cardiac function. Our objective was to determine if myocardial PKC can activate βARK1 in vivo. We studied βARK1 expression by protein immunoblotting and βARK1 activity in the hearts of transgenic mice with cardiac-specific expression of a peptide which increases αPKC activity in the heart by 50% (αPKCact) versus non-transgenic controls. Data are expressed as mean ± SEM. Results were compared using Student’s t-test. Protein expression of βARK1 in myocardial extracts was not significantly different between αPKCact and control: n = 7 in each group, P > 0.05. In contrast, βARK1 activity, as measured by its ability to phosphorylate rhodopsin, was elevated 3-fold in cardiac membrane preparations from αPKCact mice versus control: 3100 ± 214 versus 1058 ± 149 densitometry units, P < 0.05, n = 6 in each group. Based on these data, it appears that αPKC can activate βARK1 in the heart. This may be an important mechanism of βAR dysfunction in the development of myocardial hypertrophy as βARK1 is the primary GRK expressed in the heart.