alpha-Adrenergic effects on Na+-K+ pump current in guinea-pig ventricular myocytes.
alpha-Adrenergic effects on Na+-K+ pump current in guinea-pig ventricular myocytes.
复制标题
α-肾上腺素能对豚鼠心室肌细胞 Na-K 泵电流的影响。
DOI：
10.1111/j.1469-7793.1998.117bo.x
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Baldo,GJ
中科院分区：
文献类型：
--
作者：
Wang,Y;Gao,J;Mathias,RT;Cohen,IS;Sun,X;Baldo,GJ
应用全细胞膜片钳技术研究急性分离心肌细胞Na ~+-K ~+泵电流（Ip）。用普萘洛尔阻断β-肾上腺素能受体后，再用去甲肾上腺素（NA）激活α-肾上腺素能受体。Ip被测量为被毒毛旋花子苷（Str）阻断的电流。NA激活α-受体后，IP呈浓度依赖性增加。K_（0.5）依赖于细胞内[Ca ~（2+）]i，而最大刺激不依赖于细胞内[Ca ~（2+）] i。在15 nm[Ca 2 +]i处，K0.5为219 nm NA，而在1.4 μm [Ca 2 +]i处，K0.5为3 nm。在高或低[Ca ~（2+）]i时，NA均不改变Ip的电压依赖性。在每个电压下，Ip的最大刺激为14- 15%。蛋白激酶C（PKC）抑制剂Staurosporine（St）可消除α受体介导的高或低[Ca ~（2+）]i时的IP兴奋作用。对IP的刺激不依赖于细胞内钠或外部钾浓度的变化，也不反映对Str.的亲和力的变化。苯肾上腺素，甲氧胺和间羟胺，三种选择性α1-肾上腺素能激动剂，以类似于NA的方式刺激IP。NA对IP的兴奋作用可被α_1受体拮抗剂哌唑嗪所消除，但不受α_2受体拮抗剂育亨宾的影响。我们的结论是去甲肾上腺素激活心室α1-受体，其通过PKC特异性偶联以增加Na+-K+泵电流。耦合的灵敏度是[Ca ~（2+）]i依赖的，然而泵电流的最大增加是[Ca ~（2+）]i和电压无关的。
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.