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

急性心肌缺血期间细胞外钾的积累被认为是室性心律失常的主要原因，但急性冠状动脉闭塞后观察到的 K^+ 净向外运动增加的原因尚不完全清楚。细胞内 ATP 消耗导致的外向电流增加涉及缺血性心脏细胞的钾流出和动作电位持续时间 (APD) 的缩短两种磺酰脲，甲苯磺丁脲 (2 mM) 和格列本脲 (20 uM) 在豚鼠心室细胞的开放细胞贴壁斑块中以相同程度抑制 ATP 敏感 K^+ 通道的开放，这些磺酰脲类药物完全拮抗由 ATP 引起的 APD 缩短。吡那地尔 (100 uM)，一种 K^+ 通道开放剂，存在于离体豚鼠乳头肌中。然而，甲苯磺丁脲在缺氧、无葡萄糖条件下，格列本脲减少了 APD 缩短，但未能消除在缺氧、无葡萄糖条件下 APD 缩短。而格列本脲改善了狗心脏离体右心室游离壁的APD缩短，通过停止灌注而产生了实验性缺血。再次，格列本脲（20 uM）减少了心肌缺血期间的 APD 缩短，由于左冠状动脉前降支的闭塞和细胞外钾的变化，导致了心肌缺血。使用微透析法评估插入微透析管的流出物中钾和乳酸浓度的增加。在冠状动脉闭塞 30 分钟期间观察到缺血性心肌，尽管格列本脲 (1 mg/kg) 稍微降低了乳酸浓度，但未能降低流出液的钾浓度。这些结果表明，通过 ATP 敏感的外向电流增加。 K^+ 通道可能在心肌缺血期间的钾流出中不起主要作用。