Comparative effects of clarithromycin on action potential and ionic currents from rabbit isolated atrial and ventricular myocytes.
Prolongation of QT interval by several antibacterial drugs is an unwanted side effect that may be associated with development of ventricular arrhythmias. The macrolide antibacterial agent clarithromycin has been shown to cause QT prolongation. To determine the electrophysiologic basis for this arrhythmogenic potential, we investigated clarithromycin effects on (i). action potentials recorded from rabbit Purkinje fibers and atrial and ventricular myocardium using conventional microelectrodes and (ii). potassium and calcium currents recorded from rabbit atrial and ventricular isolated myocytes using whole-cell patch clamp recordings. We found that (i). clarithromycin (3-100 microM) exerted concentration-dependent lengthening effects on action potential duration in all tissues, with higher efficacy and reverse frequency-dependence in Purkinje fibers. However, clarithromycin did not cause development of early afterdepolarizations, and the parameters other than action potential duration were almost unaffected; (ii). clarithromycin (10-100 microM) reduced the delayed rectifier current. Significant blockade (approximately 30%) was found at the concentration of 30 microM. At 100 microM, it decreased significantly the maximum peak of the calcium current amplitude but failed to alter the transient outward and inwardly rectifier currents. It was concluded that these effects might be an explanation for the QT prolongation observed in some patients treated with clarithromycin.
Gluais
Pascale
P
Laboratoire de Pharmacologie, Faculté de Médecine Henri Warembourg, Pole Recherche, Lille, France. pascale_gluais@yahoo.fr
Bastide
Michìle
M
Caron
Jacques
J
Adamantidis
Monique
M
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D017291:Clarithromycin / Q000494:pharmacology*; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D007473:Ion Channels / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D016276:Ventricular Function
D007473:Ion Channels; D017291:Clarithromycin