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 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.
Gross
G J
GJ
Department of Cardiology, Children's Hospital, Boston, MA 02115, USA.
Castle
N A
NA
D000200:Action Potentials / Q000187:drug effects; D000293:Adolescent; D000375:Aging / Q000502:physiology; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D016275:Atrial Function; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects; D004553:Electric Conductivity; D005260:Female; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D018408:Patch-Clamp Techniques; D011405:Propafenone / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D011405:Propafenone