α‐Adrenergic effects on Na + ‐K + pump current in guinea‐pig ventricular myocytes

1 The whole‐cell patch clamp was employed to study Na + ‐K + pump current ( I p ) in acutely isolated myocytes. α‐Adrenergic receptors were activated with noradrenaline (NA) after blocking β‐adrenergic receptors with propranolol. I p was measured as the current blocked by strophanthidin (Str). 2 Activation of α‐receptors by NA increased I p in a concentration‐dependent manner. The K 0.5 depended on intracellular calcium ([Ca 2+ ] i ), however maximal stimulation did not. At 15 n m [Ca 2+ ] i the K 0.5 was 219 n m NA whereas at 1.4 μm [Ca 2+ ] i it was 3 n m . 3 The voltage dependence of I p was not shifted by NA at either high or low [Ca 2+ ] i . At each voltage, maximal stimulation of I p was 14‐15 %. 4 Staurosporine (St), an inhibitor of protein kinase C (PKC), eliminated the α‐receptor‐mediated stimulation of I p at either high or low[Ca 2+ ] i . 5 The stimulation of I p was independent of changes in intracellular sodium or external potassium concentrations, and did not reflect a change in affinity for Str. 6 Phenylephrine, methoxamine and metaraminol, three selective α 1 ‐adrenergic agonists, stimulate I p in a similar manner to NA. Stimulation of I p by NA was eliminated by prazosin, an α 1 ‐antagonist, but was unaffected by yohimbine, an α 2 ‐antagonist. 7 We conclude noradrenaline activates ventricular α 1 ‐receptors, which are specifically coupled via PKC to increase Na + ‐K + pump current. The sensitivity of the coupling is [Ca 2+ ] i dependent, however the maximal increase in pump current is [Ca 2+ ] i and voltage independent.