Function and regulatory mechonismes of ionic chapnels in vasculer snoock muscle cells University of Tokyo

1)为了阐明血管平滑肌细胞中由血管加压素和内皮素-1（受体介导的非选择性阳离子通道）激活的Ca^<2+> -可渗透非选择性阳离子通道的意义和特性，我们在主动脉平滑肌细胞中应用膜片钳技术、Ca^<2+>或张力测量。结果表明，这些激动剂引起的钙电和膜去极化部分是由受体介导的Ca^<2+> -可渗透非选择性阳离子通道介导的。此外，我们还展示了该通道的特性和激活机制。此外，我们还研究了细胞外Mg^<2+>和omega-3多不饱和脂肪酸对受体介导的非选择性阳离子通道的影响，这两种脂肪酸已知可产生血管松弛或降压作用。我们发现细胞外Mg^<2+>和omega-3多不饱和脂肪酸能有效抑制受体介导的非选择性阳离子通道。这可能在血管张力的调节中起重要作用。2)在气管肌细胞中，应用膜片钳技术研究Ca^<2+>依赖性Cl^-电流的激活机制和特性。我们提出Ca^<2+>依赖性Cl^-电流可被SR（肌浆网）Ca^<2+>释放激活，这是由于神经激肽A或咖啡因（通过IP_3或ryanodine受体），以及由于电压依赖性l型Ca^<2+>电流引起的Ca^<2+>注入。结果表明，ryanodine受体与电压依赖性的l型Ca^<2+>通道存在功能性偶联。

1) To clarify the significance and characterization of Ca^<2+> -permeable nonselective cation channels activated by vasopressin and endothelin-1 (receptor-mediated non-selective cation channels) in vascular smooth muscle cells, the patch clamp techniques, Ca^<2+> or tension measurement were applied in aortic smooth muscle cells. The results suggested that calcium ectry and membrane depolarization elicited by these agonists are partly mediated by a receptormediated Ca^<2+> -permeable non-selective cation channel in vascular smooth muscle cells. Also, we showed the characteristics and activation mechanisms of the channel. Furthermore, we investigated the effects of extracellular Mg^<2+> and omega-3 polyunsaturated fatty acids, which are known to produce vascular relaxation or hypotensive effects, on the receptor-mediated non-selective cation channels. We showed that extracellular Mg^<2+> and omega-3 polyunsaturated fatty acids effectively inhibit receptor-mediated non-selective cation channel. which may play an important role in the regulation of vascular tone.2) In tracheal myocytes, to investigate the activation mechanism and characterization of Ca^<2+> -dependent Cl^- current, the patch clamp technique was applied. We presented that Ca^<2+> -dependent Cl^- current can be activated by SR (sarcoplasmic reticulum) Ca^<2+> release due to neurokinin A or caffeine (through IP_3 or ryanodine receptors) as well as by Ca^<2+> infulx due to the voltage-dependent L-type Ca^<2+> current. It also showed that the functional coupling of ryanodine receptor to the voltage-dependent L-type Ca^<2+> channels exists in tracheal smooth muscle cells.