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聚被认为是室性心律失常的主要原因。然而，急性冠脉闭塞后K~(++)净外移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缩短有关。2 mM甲苯磺脲和20 mM格列本脲对开放的豚鼠心室肌细胞膜上ATP敏感性钾通道的开放有相同程度的抑制作用。这些磺脲类化合物完全拮抗K~+通道开放剂吡那地尔(100 Um)引起的豚鼠乳头肌动作电位时程缩短，而甲苯丁胺则增强缺氧、无糖状态下动作电位时程的缩短。格列本脲减少但未能废除t…在低氧、无糖状态下，动作电位时程缩短更明显。在乳头状肌暴露于含有二硝基苯酚的无葡萄糖溶液中，甲苯丁胺没有变化，而格列本脲则改善了动作电位时程缩短。在犬离体右心室游离壁制备过程中，通过冠状动脉停止充氧泰氏液灌流，造成实验性缺血。再一次，格列本脲(20um)减少了心肌缺血时的时程缩短，但不能取消时程缩短。在麻醉犬，结扎冠状动脉左前降支造成心肌缺血，用微透析法测定细胞外钾和乳酸浓度的变化。在冠脉阻断30min期间，从插入缺血心肌的微透析管流出的钾和乳酸浓度增加。格列本脲(1 mg/kg)可使出液中的乳酸浓度略有下降，但不能降低出液中的钾浓度。这些发现表明，在心肌缺血时，通过ATP敏感的K~+通道的外向电流增加可能不是钾外流的主要原因。较少

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