Myocytes from the epicardial border zone of infarcted canine hearts showed altered Vmax and a dramatic loss of the transient outward current (ito1), present in only 37% of infarcted cells vs 100% of controls.
Myocytes surviving in the infarcted canine heart exhibit significant electrophysiological alterations, including reduced Vmax and loss of the transient outward current (ito1), which may contribute to reentrant ventricular arrhythmias.
Absolute Event Rate: 37% vs 100%
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 (NZsham). 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 Vmax 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 Vmax after a depolarizing voltage clamp step was significantly altered in IZs. Using whole-cell voltage clamp techniques, we determined that the voltage-dependent, Ca(2+)-independent, 4-aminopyridine-sensitive transient outward current (ito1) occurred in all NZs (n = 16) but existed in only 37% of IZs (n = 16). There was a significant reduction in the density of ito1 elicited by depolarizing steps in those IZs showing ito1 compared with ito1 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 Vmax 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, ito1.
Lue等人（Sun）在心肌梗死（犬模型）中进行了另一项研究。评估了梗死心脏（IZs）的心肌细胞与未梗死（NZs）和假手术动物的心包心肌细胞在瞬态外向电流（ito1）存在上的差异。来自梗死犬心脏心包边缘区的心肌细胞显示出Vmax的改变，并且瞬态外向电流（ito1）显著丧失，仅在37%的梗死细胞中存在，而在100%的对照组中存在。