Electrophysiologic characterization of dronedarone in guinea pig ventricular cells

  • Gautier P
  • Guillemare E
  • Marion A
 et al. 
  • 32


    Mendeley users who have this article in their library.
  • 108


    Citations of this article.


The electrophysiological properties of dronedarone (SR33589), a noniodinated amiodarone-like agent, were studied on action potential (AP) and contraction of papillary muscle and on membrane ionic currents, Ca2+ transient, and shortening of ventricular cells of the guinea pig heart. In multicellular preparations, dronedarone (3, 10, and 30 microM) decreased maximum rate of rise of AP (dV/dt max) with a concentration- and frequency-dependent relationship; resting potential was not modified and AP amplitude was decreased only at 30 microM. The effects of dronedarone on AP durations (APDs) at different percentages of repolarization were not significantly changed, except for a slight decrease in APD30 and APD50 at the highest concentration. In isolated ventricular myocytes, dronedarone inhibited rapidly activating delayed-rectifier K+ current (I(Kr)) (median inhibitory concentration IC50 3 microM voltage-independent); slowly activating delayed-rectifier K+ current (I(Ks)) (IC50 approximately/= 10 microM voltage-dependent and time-, frequency-, or use-independent); and inward rectifier potassium current (I(K1)) (IC50 30 microM). Dronedarone blocked L-type Ca2+ current (I(Ca(L))) (IC50 = 0.18 0.018 microM at a stimulation frequency of 0.033 Hz) in a use- and frequency-dependent manner. Simultaneously to these electrophysiological effects, dronedarone reduced contraction amplitudes of papillary muscle and decreased Ca2+ transient and shortening of ventricular myocytes. The results show that dronedarone is a multichannel blocker because it decreases dV/dt max (I(Na)), I(Ca(L)), I(Kr), I(Ks), and I(K1). These effects are accompanied by a reduction in free intracellular calcium and contraction amplitudes. Dronedarone does not significantly change APD whatever the stimulation frequency. Our data demonstrate that the acute electrophysiological characteristics of dronedarone, despite absence of iodine in its molecular structure, are very similar to those of amiodarone in cardiac ventricle.

Author-supplied keywords

  • Action potential
  • Amiodarone-like
  • Contraction
  • Dronedarone
  • Electrophysiology
  • Intracellular calcium
  • Ionic currents
  • Use dependence
  • Ventricular myocytes

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document


  • Yves TourneurUniversidade Federal de Pernambuco

  • Patrick Gautier

  • Eric Guillemare

  • Aline Marion

  • Jean Philippe Bertrand

  • Dino Nisato

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free