Physiological and pharmacological study for ATP sensitive K channel in human heart

人心脏ATP敏感K通道的生理药理研究

• 批准号: 10670767
• 负责人: KATSUBE Yasuhiro
• 金额: $ 1.92万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670767/
• 关键词: human cardiac cell; ATP sensitive K channel; patch clamp; PDE inhibitor; levosimendan; イオンチャネル; カルシウム感受性増強薬

We had explored the ionic channels of human cardiac cells using whole-cell voltage clamp method. To activate the ionic channels, we used a novel Ca sensitizer, levosimendan, which has the action of opening the ATP sensitive K channel and of phosphodiesterase III inhibition. We studied about the ATP sensitive K channel mainly in 1998, and about the stimulation of L-type Ca channel through phosphodiesterase III inhibition in 1999. We found the following results.1. Levosimendan is reported to have an action of opening the ATP sensitive K channel in rat ventricular cells and mesenteric artery cells. According to our experiments, levosimendan also has the action of opening the ATP sensitive K channel in human atrial cells.2. ATP sensitive K channel was not activated in clinically relevant concentration (【approximately equal】nM), gut was activated in more high concentration such as 10 mM. These showed that levosimendan act as a cardioprotective agent by opening ATP sensitive K channels in the pathophysiological conditions such as regional ischemia.3. Levosimendan stimulated the nifedipine sensitive Ca current (L-type Ca channel) by inhibiting the phosphodiesterase III with ECィイD250ィエD2 value of 56 nM, and maximal effect was 134% of control at 1μM.These resuls were presented at the following meetings.1. 15ィイD1thィエD1 Society of Japanese Electrocardiography (1998, 10/1-2, Kagoshima)2. 35ィイD1thィエD1 Carduikiguca Paediatrica Japonica (1999, 7/7-9, Fukuoka)3. 21ィイD1stィエD1 European Society of Cardiology (1999, 8/28-9/1, Barcelona, Spain)

我们用全细胞电压钳技术研究了人心肌细胞的离子通道。为了激活离子通道，我们使用了一种新的钙敏化剂，左西孟旦，它具有开放ATP敏感性K通道和磷酸二酯酶III抑制的作用。1998年主要研究ATP敏感性钾通道，1999年研究通过磷酸二酯酶III抑制剂刺激L型钙通道。我们发现了以下结果。1.据报道，左西孟旦具有开放大鼠心室细胞和肠系膜动脉细胞中ATP敏感性K通道的作用。根据我们的实验，左西孟旦还具有开放人心房肌细胞ATP敏感性K通道的作用. ATP敏感性钾通道在临床相关浓度（[约等于]nM）下不被激活，在更高浓度（如10 mM）下肠被激活.这表明左西孟旦在病理生理条件下（如局部缺血）通过开放ATP敏感性钾通道而起到心脏保护剂的作用.左西孟旦通过抑制磷酸二酯酶III刺激硝苯地平敏感的钙电流（L型钙通道），其EC值为56 nM，在1μM时最大效应为对照的134%。15日本心电图学会第一届年会D1（1998，10/1-2，鹿儿岛）2. 35第1届世界杯D1 Carduikiguca Paediatrica Japonica（1999，7/7-9，Fukuoka）3. 21届D1欧洲心脏病学会（1999年，8/28-9/1，西班牙巴塞罗那）