Properties and role of the delayed rectifier K^+ current in the pacemaker activity

延迟整流器 K^ 电流在起搏器活动中的特性和作用

• 批准号: 11670040
• 负责人: MATSUURA Hiroshi
• 金额: $ 2.18万
• 依托单位: Shiga University of Medical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670040/
• 关键词: sino-atrial node; pacemaker activity; delayed rectifier K^+ current; I_<Kr>; I_<Ks>; maximum diastolic potential; envelope of tails test; E-4031; 心臓自動能; P2Y受容体; サイクリックGMP; サイクリックGMP依存性蛋白キナーゼ

The present research project was undertaken to investigate the properties and role of the delayed rectifier K^+ current (I_K) in isolated guinea-pig sino-atrial (SA) node pacemaker cells using the whole-cell configuration of the patchclamp technique. An envelope of tails test conducted in the absence and presence of a potent methanesulfonanilide I_<Kr> blocker E-4031 (5 μM) indicated that I_K comprises the drug-sensitive, rapidly activating and drug-resistant, slowly activating components of I_K (I_<Kr> and I_<Ks>, respectively) in guinea-pig SA node cells. The activation range for I_<Ks>, defined as the E-4031-sensitive current (half-activation voltage, V_<1/2>, of -26.2 mV) was much more negative than that for I_<Ks>, defined as the E-4031-resistant current (V_<1/2> of +17.2 mV). I_<Kr> exhibited a marked inward rectification at potentials positive to -50 mV, whereas I_<Ks> showed only a slight rectification. The tail current amplitude of I_<Kr> was comparable to that of I_<Ks>, when … More measured upon repolarization to -50 mV after a 100-ms depolarizing pulse to +20 mV, simulating an action potential. In the current-clamp experiment, a bath application of E-4031 (0.5 and 5 μM) initially delayed the repolarization phase at potentials negative to approximately -30 mV without producing any appreciable effect on repolarization at more depolarized potentials and depolarized the maximum diastolic potential in spontaneous action potentials. These results strongly indicate that the late phase of repolarization (at potentials negative to -30 mV) leading to the maximal diastolic potential at around -60 mV is primarily produced by I_<Kr> and that the contribution of I_<Kr> to the late repolarization is either absent or, if any, very small in spontaneous action potentials in guinea-pig SA node cells. While the present study did not fully elucidate the role of I_<Ks> in the spontaneous action potentials, it is reasonable to speculate that I_<Ks> is, at least in part, responsible for the early phase of repolarization in guinea-pig SA node cells. Less

本研究利用膜片钳技术的全细胞结构研究了豚鼠心房结起搏器细胞延迟整流K^+电流（I_K）的特性和作用。在甲磺酸苯胺i <Kr>阻滞剂E-4031 （5 μM）不存在和不存在的情况下进行的尾包膜试验表明，I_K在豚鼠SA结细胞中由I_K的药敏、快速激活和耐药、慢激活组分（分别为I_<Kr>和I_<Ks>）组成。I_<Ks>的激活范围，定义为e -4031敏感电流（半激活电压，V_<1/2>, -26.2 mV），远小于I_<Ks>的激活范围，定义为e -4031电阻电流（V_<1/2>, +17.2 mV）。I_<Kr>在正电位至-50 mV时表现出明显的向内整流，而I_<Ks>仅表现出轻微的整流。I_<Kr>的尾电流幅值与I_<Ks>的尾电流幅值相当，I_<Ks>的尾电流幅值与I_<Ks>的尾电流幅值相当，I_<Ks>的尾电流幅值与I_<Ks>的尾电流幅值相当。在电流箝位实验中，E-4031 （0.5 μM和5 μM）最初将负电位下的复极化相位延迟至约-30 mV，但对更多去极化电位下的复极化和自发动作电位中最大舒张电位的去极化没有明显影响。这些结果强烈表明，在豚鼠窦房结细胞的自发动作电位中，I_<Kr>对晚期复极化（负至- 30mv）产生的最大舒张电位（- 60mv左右）主要是由I_<Kr>产生的，而I_<Kr>对晚期复极化的贡献要么不存在，要么非常小。虽然目前的研究没有完全阐明I_<Ks>在自发动作电位中的作用，但我们有理由推测I_<Ks>至少部分地参与了豚鼠窦房结细胞早期复极化的发生。少

项目成果

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