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Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
10:53

Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents

Published on: July 3, 2013

Comparative effects of clarithromycin on action potential and ionic currents from rabbit isolated atrial and

Pascale Gluais1, Michìle Bastide, Jacques Caron

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

Journal of Cardiovascular Pharmacology
|March 27, 2003
PubMed

Insights

Clarithromycin prolongs the QT interval by affecting cardiac ion channels, potentially increasing arrhythmia risk. This study investigated its electrophysiologic effects on rabbit heart cells, revealing significant impacts on action potential duration and ion currents.

Area of Science:

  • Cardiology
  • Pharmacology
  • Electrophysiology

Background:

  • Antibacterial drugs, including macrolides like clarithromycin, can prolong the QT interval.
  • QT interval prolongation is linked to potentially fatal ventricular arrhythmias.

Purpose of the Study:

  • To elucidate the electrophysiologic mechanisms underlying clarithromycin-induced QT prolongation.
  • To investigate the effects of clarithromycin on cardiac action potentials and ion currents in rabbit heart tissues.

Main Methods:

  • Conventional microelectrode recordings of action potentials in Purkinje fibers, atrial, and ventricular myocardium.
  • Whole-cell patch clamp recordings of potassium (delayed rectifier) and calcium currents in isolated rabbit myocytes.
  • Concentration-dependent analysis of clarithromycin's effects (3-100 microM).

Main Results:

  • Clarithromycin dose-dependently increased action potential duration in all cardiac tissues, with notable effects in Purkinje fibers.
  • Significant reduction of the delayed rectifier potassium current (IKr) by clarithromycin.
  • Clarithromycin reduced calcium current amplitude at higher concentrations but did not affect transient outward or inwardly rectifying potassium currents.
  • No early afterdepolarizations were induced by clarithromycin.

Conclusions:

  • Clarithromycin's effects on action potential duration and ion channel currents provide a plausible explanation for QT prolongation observed in patients.
  • The reduction in delayed rectifier potassium current is a key factor in clarithromycin's proarrhythmic potential.

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