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

急性心肌缺血时细胞外钾的积累是室性心律失常的主要原因。然而，在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。本研究旨在确定细胞内ATP耗竭引起的外向电流增加是否与缺血心肌细胞钾外流和动作电位时程（APD）缩短有关。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附斑中，对ATP敏感性K^+通道开放的抑制程度相同。这些磺脲类药物完全拮抗钾通道开放剂吡那地尔（100 μ M）引起的豚鼠乳头肌APD缩短，而甲苯磺丁脲则增强缺氧无糖条件下的APD缩短。格列本脲减轻但不能消除T细胞 ...更多信息 缺氧无糖条件下APD缩短。在暴露于含二硝基苯酚的无葡萄糖溶液的乳头肌中，甲苯磺丁脲未发生变化，而格列本脲改善了APD缩短。在离体犬右心室游离壁制备中，通过停止经冠状动脉灌注含氧的台氏液来产生实验性缺血。格列本脲（20 μ M）也能减轻心肌缺血时APD缩短，但不能消除APD缩短.在麻醉犬，通过阻断冠状动脉左前降支造成心肌缺血，用微透析方法评价细胞外钾和乳酸浓度的变化。增加钾和乳酸浓度的流出物从微透析管插入到缺血心肌中观察到在冠状动脉闭塞30分钟。格列本脲（1 mg/kg）的预处理未能降低钾浓度的流出物，虽然它略有降低乳酸浓度。这些发现表明，心肌缺血时ATP敏感性K^+通道外向电流的增加可能在钾离子外流中不起主要作用。少

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