ALPHA-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 curren t (I-p) in acutely isolated myocytes. alpha-Adrenergic receptors were activated with noradrenaline (NA) after blocking beta-adrenergic recep tors with propranolol. I-p was measured as the current blocked by stro phanthidin (Str). 2. Activation of alpha-receptors by NA increased I-p in a concentration-dependent manner. The K-0.5 depended on intracellu lar calcium ([Ca2+](i)), however maximal stimulation did not. At 15 nM [Ca2+](i) the K-0.5 was 219 nM NA whereas at 1.4 mu M [Ca2+](i) it wa s 3 nM. 3. The voltage dependence of I-p was not shifted by NA at eith er high or low [Ca2+](i). At each voltage, maximal stimulation of I-p was 14-15%. 4. Staurosporine (St), an inhibitor of protein kinase C (P KC), eliminated the alpha-receptor mediated stimulation of I-p at eith er high or low [Ca2+](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, m ethoxamine and metaraminol, three selective alpha(1)-adrenergic agonis ts, stimulate I-p in a similar manner to NA. Stimulation of I-p by NA was eliminated by prazosin, an alpha(1)-antagonist, but was unaffected by yohimbine, an alpha(2)-antagonist. 7. We conclude noradrenaline ac tivates ventricular alpha(1)-receptors, which are specifically coupled via PKC to increase Na+-K+ pump current. The sensitivity of the coupl ing is [Ca2+](i) dependent, however the maximal increase in pump curre nt is [Ca2+](i) and voltage independent.