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. Who le-cell patch-clamp of enzymatically isolated atrial myocytes from 11 cardiac surgical patients aged between 29 days and 74 years revealed p otent 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 outwar d current inactivation was best described by a single exponential proc ess in the absence of propafenone and by a double exponential model in its presence. with drug-concentration-dependent acceleration of the f ast exponential component. Neither voltage dependence of steady-state transient outward current inactivation nor time course of recovery fro m inactivation was affected by propafenone. Significant inhibition (P< 0.05) of the ultra-rapidly activating delayed rectifier and inwardly r ectifying currents was observed only in the presence of greater than o r 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 pa tients of all ages. (C) 1998 Academic Press Limited.