Electrophysiologic characteristics of single myocytes isolated from hypertrophied guinea-pig hearts

Abstract

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 (200–250g). 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 ( c m) 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 c m. 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.