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

Abstract

The whole‐cell patch clamp was employed to study Na+‐K+ pump current (Ip) in acutely isolated myocytes. α‐Adrenergic receptors were activated with noradrenaline (NA) after blocking β‐adrenergic receptors with propranolol. Ip was measured as the current blocked by strophanthidin (Str). Activation of α‐receptors by NA increased Ip in a concentration‐dependent manner. The K0.5 depended on intracellular calcium ([Ca2+]i), however maximal stimulation did not. At 15 nm[Ca2+]i the K0.5 was 219 nm NA whereas at 1.4 μm [Ca2+]i it was 3 nm. The voltage dependence of Ip was not shifted by NA at either high or low [Ca2+]i. At each voltage, maximal stimulation of Ip was 14‐15 %. Staurosporine (St), an inhibitor of protein kinase C (PKC), eliminated the α‐receptor‐mediated stimulation of Ip at either high or low[Ca2+]i. The stimulation of Ip was independent of changes in intracellular sodium or external potassium concentrations, and did not reflect a change in affinity for Str. Phenylephrine, methoxamine and metaraminol, three selective α1‐adrenergic agonists, stimulate Ip in a similar manner to NA. Stimulation of Ip by NA was eliminated by prazosin, an α1‐antagonist, but was unaffected by yohimbine, an α2‐antagonist. We conclude noradrenaline activates ventricular α1‐receptors, which are specifically coupled via PKC to increase Na+‐K+ pump current. The sensitivity of the coupling is [Ca2+]i dependent, however the maximal increase in pump current is [Ca2+]i and voltage independent.

Chronic intermittent hypobaric hypoxia protects the heart against ischemia/reperfusion injury through upregulation of antioxidant enzymes in adult guinea pigs

“…Myocytes were enzymatically isolated from the left ventricles of non-CIHH or CIHH guinea pigs as previously described [26] . Briefly, guinea pigs were anesthetized with sodium pentobarbitone solution (60 mg/kg, ip).…”

Effect of resveratrol on L-type calcium current in rat ventricular myocytes

“…myocytes were obtained by using the modified enzymatic dissociation technique [12] . Male Sprague-Dawley rats (340±40 g, grade II, Certificate No 04036) were provided by the Experimental Animal Center of Hebei Province.…”

Serine 68 of phospholemman is critical in modulation of contractility, [Ca2+]itransients, and Na+/Ca2+exchange in adult rat cardiac myocytes

“…It is at present controversial as to whether I NaCa is affected by isoproterenol treatment (2,12,29). With respect to Na ϩ -K ϩ -ATPase, its activity in guinea pig ventricular myocytes was increased by PKA (11) and ␣-adrenergic stimulation, the latter presumably mediated by PKC (28). Recent evidence suggested that the putative PKA phosphorylation site (Ser 943 ) in the ␣ 1 -subunit of Na ϩ -K ϩ -ATPase (9) was internalized and not accessible to protein kinases (24).…”