Nordin C, Siri F, Aronson R S
Division of Cardiology, Albert Einstein College of Medicine, New York 10461.
J Mol Cell Cardiol. 1989 Jul;21(7):729-39. doi: 10.1016/0022-2828(89)90614-7.
To determine whether the electrical changes associated with cardiac hypertrophy are due to alterations in the membrane properties of individual hypertrophied cells, we recorded action potentials in single myocytes isolated from normal and hypertrophied hearts. Cardiac hypertrophy was produced by a gradual pressure overload created by placing a band around the ascending aorta in young guinea-pigs (200-250 g). Almost half the animals that developed left ventricular (LHV) hypertrophy also developed evidence of cardiac dysfunction. Action potentials were recorded with standard microelectrodes in single ventricular myocytes isolated by enzymatic dispersion of the heart. The action potential duration at 1 Hz was significantly longer in hypertrophied cells than in control cells. The degree of action potential prolongation in isolated cells did not correlate with the degree of hypertrophy but did correlate with the degree of myocardial disease, the duration being longer in hypertrophied myocytes from dyspneic than in those from non-dyspneic animals. The resting potential was significantly lower in hypertrophied myocytes from dyspneic animals than in hypertrophied cells from non-dyspneic animals or control cells stimulated at 5 Hz. The relationship between the frequency of stimulation (0.33, 1, and 5 Hz) and action potential duration was steeper in hypertrophied than normal myocytes. The mean membrane capacitance (cm) of hypertrophied myocytes increased by 31% over the control value. Thus, isolated hypertrophied myocytes retain the prolonged duration of the action potential and the exaggerated dependence of duration on rate observed in intact hypertrophied muscle. The increased duration of the action potential in hypertrophied cells cannot be readily attributed to the observed increase in cm. Our results indicate that the membrane changes responsible for the altered electrical properties of hypertrophied myocardium are due to an effect of hypertrophy on individual myocytes and that the prolonged duration of the action potential is probably due to changes in active currents flowing during repolarization.
为了确定与心肌肥大相关的电变化是否源于单个肥大细胞的膜特性改变，我们记录了从正常心脏和肥大心脏分离出的单个心肌细胞的动作电位。通过在幼年豚鼠（200 - 250克）的升主动脉周围放置一条束带产生逐渐的压力过载来诱导心肌肥大。几乎一半出现左心室（LHV）肥大的动物也出现了心脏功能障碍的迹象。通过酶分散心脏分离出单个心室肌细胞，用标准微电极记录动作电位。在1赫兹时，肥大细胞的动作电位持续时间明显长于对照细胞。分离细胞中动作电位延长的程度与肥大程度无关，但与心肌疾病程度相关，呼吸困难动物的肥大心肌细胞的动作电位持续时间比无呼吸困难动物的更长。呼吸困难动物的肥大心肌细胞的静息电位明显低于无呼吸困难动物的肥大细胞或5赫兹刺激的对照细胞。肥大心肌细胞中刺激频率（0.33、1和5赫兹）与动作电位持续时间之间的关系比正常心肌细胞更陡峭。肥大心肌细胞的平均膜电容（cm）比对照值增加了31%。因此，分离的肥大心肌细胞保留了完整肥大肌肉中观察到的动作电位持续时间延长以及持续时间对心率的过度依赖性。肥大细胞中动作电位持续时间的增加不能轻易归因于观察到的cm增加。我们的结果表明，导致肥大心肌电特性改变的膜变化是由于肥大对单个心肌细胞的影响，并且动作电位持续时间延长可能是由于复极化期间活动电流的变化。
