Clarithromycin reduces Isus and Ito currents in human atrial myocytes with minor repercussions on action potential

Pascale Gluais1, Michèle Bastide, Daniel Grandmougin

  • 1Laboratoire de Pharmacologie, Faculté de Médecine Henri Warembourg, Pole Recherche, 1 place de Verdun, 59045 Lille Cedex, France. pascale_gluais@yahoo.fr

Insights

The antibiotic clarithromycin prolongs action potential duration in human atrial cells by affecting specific ion currents. These direct cardiac effects may increase the risk of arrhythmias.

Area of Science:

  • Cardiology
  • Pharmacology
  • Electrophysiology

Background:

  • Macrolide antibacterial clarithromycin is known to cause QT interval prolongation.
  • Previous studies in rabbits showed clarithromycin lengthens action potential duration and blocks delayed rectifier current.

Purpose of the Study:

  • Investigate clarithromycin's effects on human atrial myocytes' ion currents (Ca2+ L-type, K+ repolarizing).
  • Assess clarithromycin's impact on action potentials in human atrial and ventricular myocardium.

Main Methods:

  • Whole-cell patch clamp recordings on human atrial myocytes.
  • Conventional microelectrode recordings from human atrial and ventricular myocardium.

Main Results:

  • Clarithromycin (10-30 microM) significantly reduced sustained outward K+ current (Isus).
  • A 100 microM concentration of clarithromycin reduced transient outward K+ current (Ito); calcium current was unaffected.
  • Clarithromycin (10-100 microM) prolonged action potential duration in atrial tissue but not ventricular tissue.

Conclusions:

  • Clarithromycin has direct cardiac electrophysiological effects.
  • These effects on ion currents and action potentials may contribute to clarithromycin's pro-arrhythmic potential.

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