Mechanisms underlying varioux regulation of Ca chammel activity in smooty muscle cells

本课题旨在阐明平滑肌细胞钙通道活性的多种调节机制。在以前的研究中，我们发现去甲肾上腺素（NE）通过两种不同的机制降低钙电流：钙依赖性失活钙通道和钙非依赖性调节。在本研究中，发现在输尿管平滑肌细胞中，NE对Ca通道的依赖性失活机制远低于输精管，在两种类型的细胞中，Ca非依赖性机制可能归因于NE诱导的花生四烯酸（AA）释放，这可能有助于减少输精管细胞的Ca电流，而不是来自输尿管。尽管外源性AA对输精管细胞Ca电流的抑制作用很大，但AA的释放是否与NE引起的Ca电流降低有关尚不清楚。AA诱导的钙电流降低不受环氧合酶抑制剂的影响 ...更多信息 e和脂氧合酶。下降是。NE对Ca激活的K电流的抑制作用大于对Ca激活的K电流的抑制作用。这导致动作电位时程的延长和收缩的增强，也证实了大量释放后细胞内的饱和钙显著减少而使钙通道活性增加的可能性。结果发现，环匹阿尼酸是一种新型的肌浆网钙泵抑制剂，经环匹阿尼酸处理后，细胞膜兴奋性增加，动作电位产生频率增加。CPA引起的变化的主要机制是钙激活钾电流的抑制。虽然没有直接证据表明细胞内钙储存位点的耗竭导致钙通道活性增强，但这种可能性也是可能的，并可能有助于膜兴奋性的增加。少

This project was undertaken to elucidate the mechanisms underlying variety oof regulation of Ca channel activity in smooth muscle cells. In previous study, we showed that norepinephrine (NE) reduces Ca current via two distinctive mechanisms ; Ca-dependent inactivation of Ca channels and Ca-independent regulation. In the present study, it was found that Ca-dependent inactivation of Ca channels mechanism in response to NE was much less available in ureter smooth muscle cells than in vas deferens in Ca-independent mechanism in two type of cells may be attributable to NE-induced release of arachidonic acid (AA) which may contribute the reduction of Ca current in cells from vas deferens but not from ureter. Although the decrease in Ca current by exogenously applied AA was large in vas deferens cells, it was not clear that the release of AA contributed to the NE-induced decrease in Ca current. The AA-induced decrease in Ca current was not affected by treatment with inhibitors of cycloxygenas … More e and lipoxygenase. The decrease was. however, partly inhibited by superoxide desmutase, indicating involvement of superoxide anion production from AA.Moreover, it became clear that NE reduced Ca-activated K current more extensively than Ca current. This resulted in the prolongation of action potentiol duration and the potentiation of contraction.The possibility was also examined that the Ca channel activity is increased by significant decrease in atored Ca in the cell after large release. It was found that memvrane excitability was increased and action potentials were more frequently generated after treatment with cyclopiazonic acid which is a novel inhibitor of Ca-pump in sarcoplasmic reticulum. The major mechanism for the CPA-induced change was the inhibition of Ca-activated K current. Although direct evidence indication ghat depletion of intracellular Ca storage sites results in the potentiation of Ca channel activity was not obtained, the possibility is also likely and may contribute to the increase in membrane excitabilyty. Less