ALTERATION OF ION CHANNELS IN VASCULAR SMOOTH MUSCLE IN HYPERTENSION

我们在1998-1999年间的研究进展总结如下：1)达尔盐敏感大鼠血管平滑肌细胞电压操作钙通道的激活增强饮食盐负荷升高达尔盐敏感大鼠血压。盐负荷后大鼠动脉平滑肌细胞表现出去极化静息膜电位和自发电活动。我们用膜片钳法证明了高盐大鼠l型钙的活化增强。在静息电位附近，激活增强尤为明显，表明这种机制有助于动脉组织的电活动增强。2)血管平滑肌细胞钠钾泵钠钾泵调节细胞内离子浓度和膜电位。我们首次采用膜片钳法对血管平滑肌细胞的Na-K泵进行了表征。Na-K泵的激活取决于胞内Na、胞外K、温度和膜电位。平滑肌钠钾泵对缬草碱敏感性高。瓦巴因对Na-K泵的抑制作用，提示Na-K泵可能参与血管平滑肌细胞的膜电位调节。3)大鼠肠系膜动脉平滑肌钾离子通道应用免疫组织化学方法对大鼠肠系膜动脉平滑肌钾离子通道进行分子鉴定。至少确定了Kv1.2、Kv1.5和Kv2.1三个组件。在膜片钳实验中，自发性高血压大鼠的电压依赖性K电流比正常对照大鼠，Wistar京都大鼠减少。

Our progress during two years (1998-1999) are summarized as follows :1) Enhanced activation of voltage-operated calcium (Ca) channels in vascular smooth muscle cells from Dahl salt sensitive ratsDietary salt loading elevates blood pressure in Dahl salt sensitive rats. Arterial smooth muscle cells exhibited depolarized resting membrane potential and spontaneous electrical activity in rats after salt loading. We demonstrated by using the patch clamp method that activation of L-type calcium was enhanced in salt-loaded rats. Enhanced activation was especially evident near the resting potential, suggesting that this mechanism would contribute enhanced electrical activity of arterial tissues.2) Sodium-potassium (Na-K) pump in vascular smooth muscle cellsNa-K pump regulates intracellular ion concentration and membrane potential. We for the first time characterized Na-K pump of vascular smooth muscle cells by using the patch clamp method. Activation of Na-K pump depended on intracellular Na, extracellular K, temperature, and membrane potential. Sensitivity to ouabain of smooth muscle Na-K pump was high. Inhibition of Na-K pump by ouabain depolarized membrane potential, suggesting that Na-K pump would contribute to regulation of membrane potential in vascular smooth muscle cells.3) Potassium (K) channels in rat mesenteric arterial smooth muscleWe performed molecular identification of voltage-dependent K channels in smooth muscle of rat mesenteric arteries by immunohistochmistry. At least three components such as Kv1.2, Kv1.5, and Kv2.1 were identified. In patch clamp experiments, voltage dependent K currents were decreased in spontaneously hypertensive rats compared to normotensive control rats, Wistar Kyoto rats.