Clarithromycin reduces Isus and Ito currents in human atrial myocytes with minor repercussions on action potential duration.
The macrolide antibacterial agent clarithromycin has been shown to cause QT interval prolongation on the electrocardiogram. In rabbit heart preparations clarithromycin (concentration dependently) lengthened the action potential duration and blocked the delayed rectifier current. The aim of the present study was to investigate the clarithromycin effects: (i) on the Ca2+ L-type and the main K+ repolarizing currents on human atrial myocytes, using whole-cell patch clamp recordings and (ii) on action potentials recorded from human atrial and ventricular myocardium using conventional microelectrodes. It has been found that (i) 10-30 microM clarithromycin reduced the sustained current Isus significantly and that a 100 microM concentration was needed to cause a significant reduction in the transient outward current Ito, whereas clarithomycin did not affect the calcium current and (ii) clarithromycin (10-100 microM) prolonged the action potential duration in atrial preparations but did not alter the different parameters of the ventricular action potential. It is concluded that clarithromycin exerts direct cardiac electrophysiological effects that may contribute to pro-arrythmic potential.
Gluais
Pascale
P
Laboratoire de Pharmacologie, Faculté de Médecine Henri Warembourg, Pole Recherche, 1 place de Verdun, 59045 Lille Cedex, France. pascale_gluais@yahoo.fr
Bastide
Michèle
M
Grandmougin
Daniel
D
Fayad
Georges
G
Adamantidis
Monique
M
D000200:Action Potentials / Q000187:drug effects*; D000368:Aged; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D020517:Atrial Appendage / Q000166:cytology / Q000187:drug effects / Q000601:surgery; D020746:Calcium Channels, L-Type / Q000187:drug effects; D002478:Cells, Cultured; D017291:Clarithromycin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D008297:Male; D008839:Microelectrodes; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology*; D011817:Rabbits; D013997:Time Factors
D000631:Aminopyridines; D020746:Calcium Channels, L-Type; D015221:Potassium Channels; D017291:Clarithromycin