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 mumol/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 > or = 10 mumol/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.