缺血对M细胞缓慢激活型延迟整流钾电流的影响
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摘要
目的：心肌细胞在电生理特性上是不均一的，在心室壁的中层存在一种电生理特性有别于心内、外膜层细胞的心肌细胞，名为M细胞。M细胞的动作电位曲线呈尖峰圆顶形；0位相最大上升速率快；1、2位相间的切迹较明显；动作电位时程较长，而且频率依赖性明显；静息电位负值较大。M细胞电生理独特性的主要离子基础是Iks电流较弱。Iks电流是心肌细胞复极的主要外向电流，它的异常变化，与心律失常的发生有很大的关系。本文拟研究缺血时心肌细胞Iks电流的变化情况。
方法：利用全细胞膜片钳方法分析急性分离的M细胞和心内、外膜细胞的Iks通道尾电流密度。利用不同成份细胞浴槽液模拟心肌细胞正常与缺血状态，并记录相应状态下Iks尾电流密度。观察缺血对Iks电流的影响。
结果：在正常状态，M细胞的Iks电流明显小于心内、外膜层细胞。在缺血状态，三层细胞的Iks电流均较正常状态明显减弱；三层细胞的Iks电流减弱程度不一，M细胞的减弱程度明显大于心内、外膜层细胞。
结论：缺血时，心肌细胞的Iks电流减弱，使得细胞动作电位复极中后期延长，容易出现EAD并引发TdP；由于M细胞的Iks电流减弱程度明显大于心内、外膜细胞，造成心室跨壁复极离散度增加，有利于折返的发生，使得心律失常得以持续。因此，增强Iks电流对控制缺血时心律失常的发生、发展是有利的。
Objective: Electrophysiological heterogeneity was observed within ventricle. A unique population of cells (M cells) exists in the midmyocardial layers of ventricle. The hallmark of the M cell: prominent spike-dome morphology of action potentials; the maximal rate of rise of the action potential upstroke; prominent phase 1 repolarization; prolongation of APD and more pronounced APD-rate relationship; decrease of the rest membrane potential. The primarily ionic basis for its electrophysiological characteristics of the M cells is a weaker Iks. Iks is the main outward current contribution to action potential repolarization. It shows a nearly relationship between abnormal Iks current and arrhythmia. In this article, I will study the effect of ischemia on Iks current of cardiac myocytes.
Methods: The whole cell recording patch clamp technique was used to investigate the Iks tail current density of enzymatic isolated M cell, sub-endocardial and sub-epicardial myocytes. Different bath solution component was used to simulate the normal and ischemic status and Iks tail current was measured under each status.
Results: Iks current was significantly smaller in M cell than in sub-endocardial myocytes or sub-epicardial under normal status. Iks current of all three layers myocytes was significantly smaller under ischemic status
?3 ?
than that under normal status. But the decrease of three layers myocytes is not in equal extent, the decrease of M cell was significantly greater than that of sub-endocardial myocytes and sub-epicardial.
Conclutions: Under ischemic condition, the decrease of Iks could prolong the mid-late repolarization phase of APD. It could cause BAD and then arouse TdP. Because the decrease of M cell was significantly greater than that of sub-endocardial myocytes and sub-epicardial myocytes, it could increase TDR. Cardiac arrhythmias could last due to reentrance that secondary the increase of TDR. So, to increase Iks current is a good idea to control the occurring and development of cardiac arrhythmias.
方法：利用全细胞膜片钳方法分析急性分离的M细胞和心内、外膜细胞的Iks通道尾电流密度。利用不同成份细胞浴槽液模拟心肌细胞正常与缺血状态，并记录相应状态下Iks尾电流密度。观察缺血对Iks电流的影响。
结果：在正常状态，M细胞的Iks电流明显小于心内、外膜层细胞。在缺血状态，三层细胞的Iks电流均较正常状态明显减弱；三层细胞的Iks电流减弱程度不一，M细胞的减弱程度明显大于心内、外膜层细胞。
结论：缺血时，心肌细胞的Iks电流减弱，使得细胞动作电位复极中后期延长，容易出现EAD并引发TdP；由于M细胞的Iks电流减弱程度明显大于心内、外膜细胞，造成心室跨壁复极离散度增加，有利于折返的发生，使得心律失常得以持续。因此，增强Iks电流对控制缺血时心律失常的发生、发展是有利的。
Objective: Electrophysiological heterogeneity was observed within ventricle. A unique population of cells (M cells) exists in the midmyocardial layers of ventricle. The hallmark of the M cell: prominent spike-dome morphology of action potentials; the maximal rate of rise of the action potential upstroke; prominent phase 1 repolarization; prolongation of APD and more pronounced APD-rate relationship; decrease of the rest membrane potential. The primarily ionic basis for its electrophysiological characteristics of the M cells is a weaker Iks. Iks is the main outward current contribution to action potential repolarization. It shows a nearly relationship between abnormal Iks current and arrhythmia. In this article, I will study the effect of ischemia on Iks current of cardiac myocytes.
Methods: The whole cell recording patch clamp technique was used to investigate the Iks tail current density of enzymatic isolated M cell, sub-endocardial and sub-epicardial myocytes. Different bath solution component was used to simulate the normal and ischemic status and Iks tail current was measured under each status.
Results: Iks current was significantly smaller in M cell than in sub-endocardial myocytes or sub-epicardial under normal status. Iks current of all three layers myocytes was significantly smaller under ischemic status
?3 ?
than that under normal status. But the decrease of three layers myocytes is not in equal extent, the decrease of M cell was significantly greater than that of sub-endocardial myocytes and sub-epicardial.
Conclutions: Under ischemic condition, the decrease of Iks could prolong the mid-late repolarization phase of APD. It could cause BAD and then arouse TdP. Because the decrease of M cell was significantly greater than that of sub-endocardial myocytes and sub-epicardial myocytes, it could increase TDR. Cardiac arrhythmias could last due to reentrance that secondary the increase of TDR. So, to increase Iks current is a good idea to control the occurring and development of cardiac arrhythmias.
引文
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2. Drouin E, Charpentier F, Gauthier C, et al. Evidence for the presence of M cells in the human ventricle. PACE, 1993,16:876-876
3. Drouin E, Charpentier F, Gauthier C, et al. Electrophysiologic characteristic of cells spanning the left ventricular wall of human heart: evidence for presence of M cells. J Am Coll Cardiol, 1995,26:185-192
4. Antzelevitch C, Sicouri S. Clinical relevance of cardiac arrhythmias generated by afterdepolarizations: the role of Mcells in the generation of U waves, triggered activity and torsade de points. J Am Coil Cardiol, 1994,23:259-277
5. Antzelevitch C, Nesterenko VV, Yan GX. Role of M cells in acquired long QT syndrome, U waves, and Torsade de pointes, J Electrocardiol, 1995,28(suppl): 131-138
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