Propafenone inhibition of human atrial myocyte repolarizing currents

This study was aimed at defining cellular electropharmacologic effects of propafenone on repolarizing currents in human atrial myocytes. Whole-cell patch-clamp of enzymatically isolated atrial myocytes from 11 cardiac surgical patients aged between 29 days and 74 years revealed potent time- and concentration-dependent (IC50 = 4.8 +/- 0.4 mu mol/l), but age-, voltage-, and frequency-independent propafenone inhibition of transient outward current. Time course of apparent transient outward current inactivation was best described by a single exponential process in the absence of propafenone and by a double exponential model in its presence. with drug-concentration-dependent acceleration of the fast exponential component. Neither voltage dependence of steady-state transient outward current inactivation nor time course of recovery from inactivation was affected by propafenone. Significant inhibition (P<0.05) of the ultra-rapidly activating delayed rectifier and inwardly rectifying currents was observed only in the presence of greater than or equal to 10 mu mol/l propafenone. These actions of propafenone could explain its repolarization prolonging effect and might contribute to clinical electrophysiologic responses which have been documented in patients of all ages. (C) 1998 Academic Press Limited.