α-Adrenergic regulation of phosphoinositide metabolism and protein kinase C in isolated cardiac myocytes

α₁-Adrenergic regulation of phosphoinositide metabolism and protein kinase C translocation was studied in isolated rat cardiac myocytes. Exposure of [³H]inositol-labeled myocytes to norepinephrine in the presence of propranolol caused a dose-dependent increase in [³H]inositol phosphates. Norepinephrine also increased the level of membrane-associated protein kinase C from ~10% of total activity to 18%, with a dose response similar to that for generation of inositol phosphates. Depolarization of myocytes with 30 mM KCl had no effect on inositol phosphates or membrane-associated protein kinase C but potentiated the effect of submaximal norepinephrine on both parameters. The potentiation of protein kinase C translocation was amplified when extracellular Ca²⁺ was increased to 4 mM, resulting in membrane association of one-third of the total cellular activity. These data show that activation of protein kinase C occurs during α₁-adrenergic stimulation of cardiac myocytes and that elevation of intracellular Ca²⁺ amplifies this effect at least in part through increased phosphoinositide metabolism.