Effects of mexiletine on action potentials of guinea-pig right ventricular papillary muscles

The effects og mexiletine on transmembrane potentials were studied in guinea-pig right ventricular papillary muscles, using conventional microelectrode techniques. The voltage-dependent and frequency -dependent effects were studied by using 3 kinds of external K^＋ solutions (RMP were nearly -101. -86 and -68mV), and by changing the stimulation frewuency from 0.1 to 4 Hz. The depression of Vmax by 20μmol/l mexiletine was increased significantly as RMP was decreased and stimulation frequency was increased, but ‘two-step’ process of h-curve was not recognized. The time course of recovery of Vmax, which was studied by applying premature stimuli during diastolic intervals, was fitted to a monoexponential function, using a non-linear least squares method. Zero time-interceots were significantly increased by reducing RMP (P＜0.01, n＝5), where-as time constants were not dhanged significantly. The reduction of Vmax at high frequencies and the zero time-intercept in the recovery time course of Vmax were decreased when the action potential duration was shortened by the addition of 1mmol/l nicorandil. Such dependence of the effects of mexiletine on APD indicates higher affinity of mexiletine for inactivated channel state than for activated state. Much prolongation of ERP by mexiletine may be the result og this property.