Huelsing Delilah J, Spitzer Kenneth W, Pollard Andrew E
Cardiac Rhythm Management Lab, Department of Biomedical Engineering, University of Alabama-Birmingham, Volker Hall B140, 1670 University Blvd., Birmingham, AL 35294, USA.
Cardiovasc Res. 2003 Sep 1;59(3):620-7. doi: 10.1016/s0008-6363(03)00507-8.
The development of an "injury current" secondary to heterogeneous ion accumulation and cellular uncoupling across the ischemic border zone has been implicated as a trigger for arrhythmias arising during acute ischemia. The purpose of the present study was to determine the effects of injury current across the Purkinje-ventricular interface in the development of abnormal automaticity.
Patch clamp and electronic cell coupling techniques were used to record action potentials from and to apply injury current to isolated rabbit Purkinje myocytes. Injury current was dependent upon: (1) a coupling resistance, which was varied to simulate different degrees of cellular uncoupling, and (2) the difference in Purkinje membrane potential and depolarized ischemic myocardium, which was represented by a passive resistor-capacitor circuit with initial voltages of -70, -60, or -50 mV.
During coupling to the moderately depolarized cell (-60 or -50 mV), Purkinje myocytes developed repetitive, spontaneous activity within a window of coupling resistances. This abnormal automaticity was dependent upon L-type calcium current, as cadmium or nifedipine completely suppressed coupling-induced spontaneous activity.
Our results demonstrate that injury current alone can induce spontaneous activity in normal Purkinje myocytes. The level of myocardial depolarization and the degree of cellular uncoupling required to induce this activity suggest spontaneous Purkinje activity induced by injury current as a potent trigger for acute ischemic arrhythmias.
缺血边界区内离子异质性积聚和细胞解偶联所导致的“损伤电流”被认为是急性缺血期间心律失常的触发因素。本研究的目的是确定跨浦肯野纤维 - 心室界面的损伤电流在异常自律性形成中的作用。
采用膜片钳和电子细胞偶联技术记录离体兔浦肯野细胞的动作电位，并向其施加损伤电流。损伤电流取决于：（1）偶联电阻，改变该电阻以模拟不同程度的细胞解偶联；（2）浦肯野细胞膜电位与去极化缺血心肌之间的电位差，由初始电压为 -70、-60 或 -50 mV 的无源电阻 - 电容电路表示。
在与中度去极化细胞（-60 或 -50 mV）偶联期间，浦肯野细胞在一定范围的偶联电阻内产生重复性自发活动。这种异常自律性依赖于 L 型钙电流，因为镉或硝苯地平可完全抑制偶联诱导的自发活动。
我们的结果表明，仅损伤电流就能在正常浦肯野细胞中诱导自发活动。诱导这种活动所需的心肌去极化水平和细胞解偶联程度表明，损伤电流诱导的浦肯野细胞自发活动是急性缺血性心律失常的一个重要触发因素。
