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1The effect of cardiac hypertrophy on electrocardiogram (ECG), action potential duration (APD) and repolarizing K+currents was investigated in epicardial, midmyocardial and endocardial myocytes isolated from the rat left ventricular free wall.2Cardiac hypertrophy was induced by stenosis of the ascending aorta (AS), which led to an increased pressure load (+85 ± 10 mm) of the left ventricle; sham‐operated animals served as controls.3In ECG recordings from AS rats, the QTc interval was prolonged and the main vectors of the QRS complex and the T‐wave pointed in opposite directions, indicating an abnormal sequence of repolarization.4APD and K+currents were recorded using the whole‐cell patch‐clamp technique. In the AS group, APD90(90 % repolarization) was significantly prolonged in epicardial and midmyocardial, but not endocardial myocytes.5Corresponding to the increase in APD, the magnitude of the transient outward K+current (Ito1) was significantly smaller (‐30 %) in epicardial and midmyocardial, but not endocardial myocytes.6Inactivation and steady‐state inactivation of Ito1were not affected by hypertrophy. Recovery from inactivation was slightly prolonged in endocardial myocytes from AS rats.7No differences in delayed rectifier currents (IK) or inwardly rectifying K+currents (IK1) were detected between myocytes of the three regions of sham‐operated or AS animals. However, both currents were reduced by AS.8The present data show that cardiac hypertrophy caused by pressure overload leads to an increase in APD and a decrease in Ito1primarily in epicardial and midmyocardial myocytes, which implies a major role of alterations in Ito1for the reduced gradient in APD. The effects of AS on IK1and IKmay slightly counteract the decrease in APD gradient. The observed changes in APD and underlying ionic currents could well explain the alterations in repolarization observed in the ECG induced by cardiac hypertrophy.

1The transient outward K+current (Ito) is a major repolarizing ionic current in ventricular myocytes of several mammals. Recently it has been found that its magnitude depends on the origin of the myocyte and is regulated by a number of physiological and pathophysiological signals.2The relationship between the magnitude of Ito, action potential duration (APD) and Ca2+influx (QCa) was studied in rat left ventricular myocytes of endo‐ and epicardial origin using whole‐cell recordings and the action potential voltage‐clamp method.3Under control conditions, in response to a depolarizing voltage step to +40 mV, Itoaveraged 12.1 ± 2.6 pA pF−1in endocardial (n= 11) and 24.0 ± 2.6 pA pF−1in epicardial myocytes (n= 12; P< 0.01). APD90(90 % repolarization) was twice as long in endocardial myocytes, whereas QCainversely depended on the magnitude of Ito. L‐type Ca2+current density was similar in myocytes from both regions.4To determine the effects of controlled reductions of Itoon QCa, recordings were repeated in the presence of increasing concentrations of the Itoinhibitor 4‐aminopyridine.5Inhibition of Itoby as little as 20 % more than doubled QCain epicardial myocytes, whereas it had only a minor effect on QCain myocytes of endocardial origin. Further inhibition of Itoled to a progressive increase in QCain epicardial myocytes; at 90 % inhibition of Ito, QCawas four times larger than the control value.6We conclude that moderate changes in the magnitude of Itostrongly affect QCaprimarily in epicardial regions. An alteration of Itomight therefore allow for a regional regulation of contractility during physiological and pathophysiological adaptations.