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Possible Involvement of Increased Outward K^+ Current Induced by Intracellular Metabolic Derangement in Extracellular K^+ Accumulation during Myocardial Ischemia.

心肌缺血期间细胞内代谢紊乱引起的外向 K^ 电流增加可能与细胞外 K^ 积累有关。

基本信息

批准号：
63570085
负责人：
NAKAYA Haruaki
金额：
$ 1.34万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

项目摘要

Extracellular potassium accumulation during acute myocardial ischemia has been implicated as a major cause of ventricular arrhythmias. However, the cause of the increased net outward movement of K^+ observed after acute coronary occlusion is not fully understood. This study was undertaken to determine whether an increase in outward current resulting from depletion of intracellular ATP is involved in potassium efflux from ischemic heart cells and a shortening of action potential duration (APD). Two sulfonyl-ureas, tolbutamide (2 mM) and glibenclamide (20 uM) inhibited the openings of the ATP- sensitive K^+ channels to the same extent in the open cell-attached patch of guinea-pig ventricular cells. These sulfonylureas completely antagonized the APD shortening induced by pinacidil (100 uM), a K^+ channel opener, in isolated guinea-pig papillary muscles.However, tolbutamide potentiated the APD shortening in the hypoxic, glucose-free condition. Glibenclamide lessened but failed to abolish t … More he APD shortening in the hypoxic, glucose-free condition. In the papillary muscles exposed to a glucose-free solution containing dinitrophenol, tolbutamide unchanged while glibenclamide improved the APD shortening. In isolated right ventricular free wall preparation of the dog heart, experimental ischemia was produced by discontinuing the perfusion with oxygenated Tyrode solution through the coronary artery. Again, glibenclamide (20 uM) lessened but failed to abolish the APD shortening during myocardial ischemia. In anesthetized dogs, myocardial ischemia was produced by occlusion of the left anterior descending coronary artery, and changes in extracellular potassium and lactate concentrations were evaluated using micro- dialysis method. Increases in potassium and lactate concentrations of the effluent from the microdialysis tubes inserted into the ischemic myocardium were observed during coronary occlusion of 30 min. Pretreatment with glibenclamide (1 mg/kg) failed to decrease the potassium concentration of the effluent although it slightly decreased the lactate concentration. These findings suggest that an increase in outward current through ATP-sensitive K^+ channels may not play a major role in the potassium efflux during myocardial ischemia. Less

急性心肌缺血期间的细胞外钾积累已被认为是室性心律失常的主要原因。然而，急性冠状动脉闭塞后观察到的K^+净向外移动增加的原因尚不完全清楚。本研究旨在确定由细胞内ATP耗竭引起的向外电流增加是否与缺血心脏细胞的钾外排和动作电位持续时间（APD）缩短有关。两种磺胺脲，甲苯丁酰胺（2 mM）和格列本脲（20 uM）对豚鼠心室细胞开放贴壁中ATP敏感的K^+通道的开放有相同程度的抑制作用。在离体豚鼠乳头肌中，这些磺脲类药物完全拮抗由K^+通道打开剂pinacidil （100 uM）诱导的APD缩短。然而，在缺氧、无葡萄糖的情况下，甲苯丁胺增强了APD的缩短。格列本脲对缺氧、无糖状态下APD缩短有明显的抑制作用。在乳头肌暴露于含二硝基苯酚的无葡萄糖溶液中，甲磺丁酰胺不变，而格列本脲则改善了APD缩短。在离体犬心脏右心室无壁制备中，用氧合Tyrode溶液经冠状动脉停止灌注造成实验性缺血。同样，格列本脲（20um）减少但未能消除心肌缺血时APD缩短。麻醉犬左冠状动脉前降支闭塞引起心肌缺血，用微透析法观察细胞外钾和乳酸浓度的变化。在冠状动脉闭塞30分钟时，观察到插入缺血心肌的微透析管流出物中钾和乳酸浓度的增加。格列苯脲预处理（1mg /kg）虽能降低乳酸浓度，但不能降低出水钾浓度。这些发现表明，通过atp敏感的K^+通道的向外电流的增加可能在心肌缺血期间钾外溢中不起主要作用。少