DIMINISHED TRANSIENT OUTWARD CURRENTS IN RAT HYPERTROPHIED VENTRICULAR MYOCYTES

Action potential duration is prolonged in ventricular hypertrophy induced by sustained pressure overload. Since the transient outward current (I-to) is a major factor for determining action potential duration in rat ventricular cells, we used patch-clamp techniques to compare the characteristics of I-to in normal and hypertrophied left ventricular cells of the rat. Left ventricular pressure overload was induced by partial ligation of the abdominal aorta for 4 to 6 weeks before study. Age-matched normal rats served as controls. Pressure overload increased the heart weight-to-body weight ratio by 47.7%. I-to was significantly smaller in hypertrophied cells than in normal cells (20.0+/-1.3 versus 31.0+/-2.1 pA/pF, respectively, at a test potential of +60 mV; P<.001). There were no differences in the steady-state inactivation, the inactivation time course, and the time course of recovery from inactivation between normal and hypertrophied cells. At the single-channel level, there were no differences in the unitary current amplitude of the single I-to channel between normal and hypertrophied cells, and the slope conductance was 13.7 picosiemens in normal cells and 13.4 picosiemens in hypertrophied cells. The maximum open-state probability, which was estimated from the ratio of the peak of the ensemble-averaged currents to the single-channel current amplitude, was similar for normal and hypertrophied cells (0.66+/-0.03 and 0.69+/-0.04, respectively, at a test potential of +40 mV; P=NS). We conclude that diminished I-to contributes to action potential prolongation in hypertrophied ventricular cells from pressure-overloaded rat hearts. Reduced I-to channel density may be responsible for the diminished whole-cell I-to.