Baiardi Gustavo, Zumino Amira Ponce, Petrich Elena Ruiz
Department of Morphophysiology, University of Cuyo, Mendoza, Argentina.
Mol Cell Biochem. 2003 Dec;254(1-2):185-91. doi: 10.1023/a:1027384215339.
The aim of this work was to investigate the role of the inward rectifying (K1) and the sarcolemmal ATP-sensitive K+ (K-ATP) channels in the electrical response to regional ischemia and the subsequent development of ventricular tachyarrhythmias on reflow (RA). Surface electrograms (ECG) and the transmembrane potential from subepicardial left ventricular cells were recorded in spontaneously beating rat hearts perfused with buffer alone (controls) or exposed to 100 microM BaCl2 or 100 microM 5-hydroxydecanoate (5-HD) to block either K1 or K-ATP channels respectively. After 20 min of equilibration and 10 min of control recordings, the left anterior descending coronary artery was occluded for 10 min. This was followed by reperfusion. The effects of regional ischemia as well as those of reperfusion (10 min) were recorded throughout. In the three groups, ischemia induced a modest decrease in heart rate and a sharp reduction in resting potential within 3 min. The latter as well as the accompanying depression of propagated electrical activity were enhanced by Ba2+. A partial recovery of the resting potential was observed in all groups during the last 2 min of coronary occlusion. Concomitantly, a slight reduction in the action potential duration was found in the control hearts. This effect was blocked by 5-HD. Under Barium the action potential duration increased by a factor of 3 and its ischemic variations were minimized. Severe sustained ventricular tachyarrhythmias developed on reflow in the controls and in the 5-HD exposed hearts. Barium limited the duration of arrhythmic episodes to a few seconds. Our data indicate that the initial electrical effects of ischemia are unrelated to activation of ATP sensitive K+ channels and that gK1 dominates the K+ membrane conductance at this stage. Furthermore, they show that action potential lengthening limits the duration of arrhythmic episodes triggered by reperfusion. This suggests that electrical heterogeneity plays an important role in the perpetuation of reperfusion arrhythmias.
本研究旨在探讨内向整流（K1）通道和肌膜ATP敏感性钾（K-ATP）通道在局部缺血电反应以及再灌注（RA）后室性快速心律失常后续发展中的作用。在单独用缓冲液灌注（对照组）或分别暴露于100微摩尔氯化钡或100微摩尔5-羟基癸酸（5-HD）以阻断K1或K-ATP通道的自发搏动大鼠心脏中，记录体表心电图（ECG）和左心室心外膜下细胞的跨膜电位。平衡20分钟并进行10分钟对照记录后，闭塞左前降支冠状动脉10分钟。随后进行再灌注。全程记录局部缺血以及再灌注（10分钟）的影响。在三组中，缺血在3分钟内导致心率适度下降和静息电位急剧降低。钡离子增强了后者以及伴随的传导性电活动抑制。在冠状动脉闭塞的最后2分钟内，所有组均观察到静息电位部分恢复。同时，在对照心脏中发现动作电位时程略有缩短。该效应被5-HD阻断。在钡离子作用下，动作电位时程增加了3倍，其缺血变化最小化。对照组和暴露于5-HD的心脏在再灌注时出现严重的持续性室性快速心律失常。钡离子将心律失常发作的持续时间限制在几秒内。我们的数据表明，缺血的初始电效应与ATP敏感性钾通道的激活无关，并且在此阶段gK1主导钾膜电导。此外，它们表明动作电位延长限制了再灌注引发的心律失常发作的持续时间。这表明电不均一性在再灌注心律失常的持续存在中起重要作用。
