Thuringer D, Coulombe A, Deroubaix E, Coraboeuf E, Mercadier J J
Laboratoire de Cardiologie Moléculaire et Cellulaire, Université de Paris, France.
J Mol Cell Cardiol. 1996 Feb;28(2):387-401. doi: 10.1006/jmcc.1996.0036.
We determined whether the dilated cardiomyopathy which develops between 30 and 140 days of age in the Syrian hamster strain MS200, before the onset of cardiac hypertrophy and failure, is associated with alterations in both the action potential (AP) and the Ca(2+)-independent transient outward current, Ito1. AP was recorded in perfused hearts using microelectrodes and Ito1 was recorded in single ventricular myocytes using the whole-cell patch-clamp. The MS200 strain was compared to the control CHF148 strain at different periods of age (60, 90, 120 and 180 days). APs were markedly lengthened in MS200 compared to CHF148 hearts at all ages studied. Cell membrane capacitance increased with age in the two strains, but was not significantly higher in MS200 than in CHF148 of a given age, indicating the absence of cell hypertrophy. At 60 days of age, Ito1 density was the same in the two strains. Later on, Ito1 density increased markedly at 90-120 days then decreased at 180 days in CHF148, whereas this increase was delayed and of reduced amplitude in MS200. The sustained component of outward current, Isus, was not sizeably different in the two strains. The conductance-voltage and steady-state inactivation relationships were shifted with age towards positive potentials by 15 mV in the two strains, but earlier in MS200 (90 days) than in CHF148 (180 days). Similarly, the recovery of Ito1 from inactivation exhibited a slow component which increased with age in the two strains but was larger in MS200 than in CHF148. In conclusion, alterations of Ito1 may contribute to changes in shape of AP, but cannot entirely explain dilation-induced AP lengthening.
我们确定了叙利亚仓鼠MS200品系在30至140日龄之间、在心脏肥大和衰竭发生之前出现的扩张型心肌病，是否与动作电位（AP）和钙非依赖性瞬时外向电流Ito1的改变有关。使用微电极在灌注心脏中记录AP，使用全细胞膜片钳在单个心室肌细胞中记录Ito1。在不同年龄阶段（60、90、120和180天）将MS200品系与对照CHF148品系进行比较。在所有研究年龄中，与CHF148心脏相比，MS200心脏中的AP明显延长。两个品系的细胞膜电容均随年龄增加，但在给定年龄下，MS200的细胞膜电容并不显著高于CHF148，表明不存在细胞肥大。在60日龄时，两个品系的Ito1密度相同。此后，CHF148品系在90 - 120天时Ito1密度显著增加，然后在180天时下降，而MS200品系中这种增加出现延迟且幅度减小。外向电流的持续成分Isus在两个品系中没有显著差异。两个品系的电导 - 电压和稳态失活关系均随年龄向正电位方向偏移15 mV，但MS200（90天）比CHF148（180天）更早出现这种偏移。同样，Ito1从失活状态恢复时表现出一个缓慢成分，两个品系中该成分均随年龄增加，但MS200中的比CHF148中的更大。总之，Ito1的改变可能导致AP形状的变化，但不能完全解释扩张引起的AP延长。
