ABNORMAL ELECTRICAL-PROPERTIES OF MYOCYTES FROM CHRONICALLY INFARCTED CANINE HEART - ALTERATIONS IN VMAX AND THE TRANSIENT OUTWARD CURRENT
ABNORMAL ELECTRICAL-PROPERTIES OF MYOCYTES FROM CHRONICALLY INFARCTED CANINE HEART - ALTERATIONS IN VMAX AND THE TRANSIENT OUTWARD CURRENT
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DOI：
10.1161/01.cir.85.3.1175
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发表时间：
1992-03-01
期刊：
影响因子：
37.8
通讯作者：
BOYDEN, PA
中科院分区：
文献类型：
--
作者：
LUE, WM;BOYDEN, PA
背景。冠状动脉闭塞后5天，犬心脏心外膜边缘区残存肌纤维可发生重入性室性心律失常。为了了解这些心律失常的细胞基础，我们开发了一种从心外膜边界区分散肌细胞（IZs）的方法。方法与结果。我们比较了IZs与对照非梗死动物（NZs）和假手术动物（NZ(sham)）心外膜分散细胞的电生理特性。与NZs相比，IZs的跨膜动作电位在总动作电位振幅和最大上冲程速度上均有所降低。然而，IZs的静息电位与NZs没有什么不同。与对照组相比，-10 mV动作电位持续时间显著减少，并且IZ电位没有表现出在所有NZs中明显的典型的“尖峰和圆顶”形态。使用V（max）作为动作电位上冲程可用的内向电流峰值的间接度量，我们发现IZs的可用性曲线与NZ曲线显着不同。此外，在去极化电压箝位后恢复V（max）的时间过程显著改变。利用全细胞电压钳技术，我们确定了电压依赖性、Ca2+依赖性、4-氨基吡啶敏感的瞬时外向电流（i(to1)）发生在所有NZs （n = 16）中，但仅存在于37%的IZs （n = 16）中。在显示i（to1）的IZs中，与nzs中的i（to1）密度相比，去极化步骤引起的i（to1）密度显著降低。我们已经开发出了在梗死心脏中存活的单细胞模型。我们的研究表明，在IZs中有V（max）的变化。此外，在IZ动作电位中没有明显的1相复极化。这与负责电压依赖性瞬态向外电流i（to1）的离子通道功能的显著损失是一致的。
Background. Reentrant ventricular arrhythmias can occur in the surviving muscle fibers of the epicardial border zone of the canine heart 5 days after coronary artery occlusion. To understand the cellular basis of these arrhythmias, we developed a method of dispersing myocytes (IZs) from the epicardial border zone.Methods and Results. We compared the electrophysiological properties of IZs with those of cells dispersed from the epicardium of control noninfarcted (NZs) and of sham-operated animals (NZ(sham)). Transmembrane action potentials of IZs are reduced in total action potential amplitude and maximum upstroke velocity compared with NZs. However, resting potential of IZs is no different from that of NZs. Action potential duration at -10 mV is significantly reduced in IZs compared with control, and IZ potentials do not show the typical "spike and dome" morphology that is evident in all NZs. Using V(max) as an indirect measure of the peak inward current available for the upstroke of the action potential, we found that the availability curve for IZs is significantly different from the NZ curve. Furthermore, the time course of recovery of V(max) after a depolarizing voltage clamp step was significantly altered in IZs. Using whole-cell voltage clamp techniques, we determined that the voltage-dependent, Ca2+-independent, 4-aminopyridine-sensitive transient outward current (i(to1)) occurred in all NZs (n = 16) but existed in only 37% of IZs (n = 16). There was a significant reduction in the density of i(to1) elicited by depolarizing steps in those IZs showing i(to1) compared with i(to1) density in NZs.Conclusions. We have developed a single-cell model of cells that survive in the infarcted heart. Our studies indicate that there are changes in V(max) in IZs. In addition, there is no prominent phase 1 of repolarization in IZ action potentials. This is consistent with the dramatic loss in the function of the ionic channel responsible for the voltage-dependent transient outward current, i(to1).