Thuringer D, Deroubaix E, Coulombe A, Coraboeuf E, Mercadier J J
Laboratoire de Cardiologie Moléculaire et Cellulaire, Université de Paris XI, France.
Cardiovasc Res. 1996 May;31(5):747-57. doi: 10.1016/0008-6363(96)00018-1.
The aim of our study was to determine the main electrophysiological alterations associated with cardiac dilation in MS200 strain Syrian hamsters, a model of genetically determined cardiomyopathy.
Ventricular action potentials (APs) were recorded with standard microelectrodes in isolated hearts from 120-day-old cardiomyopathic (strain MS200) and age-matched control (strain CHF148) Syrian hamsters. Ionic currents were recorded from single ventricular myocytes using the whole-cell patch-clamp technique.
In MS200, AP was prolonged and the plateau phase was markedly increased as compared to CHF148. Differences in both AP duration and 4-aminopyridine-induced AP lengthening between epicardial and endocardial tissues were less marked in MS200 than in CHF148 ventricles. Cell size and membrane capacitance were not higher in MS200 than in CHF148 myocytes, indicating the absence of cell hypertrophy in myopathic ventricles. The L-type calcium current (ICa,L) density was significantly reduced in MS200 and the voltage-dependence of both steady-state activation and inactivation was altered. The voltage-dependent outward current was composed of both transient (Ito1) and sustained (Iss) components, respectively sensitive and insensitive to 4-aminopyridine. Ito1 density was strongly depressed in MS200 compared to CHF148, whereas Iss density was only slightly reduced. The conductance-voltage and steady-state inactivation relationships for Ito1 were shifted to more positive potentials in MS200. The Ito1 recovery process was markedly slower in MS200 than in CHF148. The steady-state current-voltage relationships, in the physiological voltage range, were superimposable in MS200 and CHF148.
In ventricular myocytes from dilated heart of MS200 Syrian hamsters, Ito1 is more drastically depressed than ICa,L. Such an observation might partially explain dilation-induced AP lengthening.
我们研究的目的是确定与MS200品系叙利亚仓鼠心脏扩张相关的主要电生理改变，该品系是一种基因决定的心肌病模型。
用标准微电极记录120日龄心肌病（MS200品系）和年龄匹配的对照（CHF148品系）叙利亚仓鼠离体心脏的心室动作电位（AP）。使用全细胞膜片钳技术记录单个心室肌细胞的离子电流。
与CHF148相比，MS200中AP延长且平台期明显延长。MS200中心外膜和心内膜组织之间的AP持续时间和4-氨基吡啶诱导的AP延长的差异比CHF148心室中不明显。MS200中的细胞大小和膜电容并不高于CHF148中的心肌细胞，表明病变心室中不存在细胞肥大。MS200中L型钙电流（ICa,L）密度显著降低，稳态激活和失活的电压依赖性均发生改变。电压依赖性外向电流分别由瞬时（Ito1）和持续（Iss）成分组成，分别对4-氨基吡啶敏感和不敏感。与CHF148相比，MS200中Ito1密度强烈降低，而Iss密度仅略有降低。MS200中Ito1的电导-电压和稳态失活关系向更正电位偏移。MS200中Ito1的恢复过程明显比CHF148中慢。在生理电压范围内，MS200和CHF148中的稳态电流-电压关系可叠加。
在MS200叙利亚仓鼠扩张心脏的心室肌细胞中，Ito1比ICa,L更显著降低。这一观察结果可能部分解释了扩张诱导的AP延长。
