ALPHA-1-ADRENERGIC STIMULATION OF NA-H EXCHANGE IN CARDIAC MYOCYTES

The activation of Na-H exchange in adult rat heart myocytes was characterized in response to a phorbol ester (phorbol 12-myristate 13-acetate) and an alpha1-adrenergic agonist [6-fluoronorepinephrine (6F-NE)]. Transport activation was assessed by determining the initial rate with which intracellular pH (pH(i)) was returned from an acid pulse and by following changes in steady-state pH(i); pH(i) was determined by a pH-sensitive fluorescent dye. Both agonists shifted the intracellular pH dependence of Na-H exchange by 0.10-0.15 pH units in the alkaline direction. This shift was prevented by the presence of sphingosine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), inhibitors of protein kinase C. The agonists also alkalinized pH(i) at steady state. The alkalinization by 6F-NE was blocked by prazosin and H-7. This indicates that the adrenergic stimulation of cardiac Na-H exchange is mediated by an al-adrenergic mechanism and very likely involves the activation of protein kinase C.