Electrophysiological mechanisms of sophocarpine as a potential antiarrhythmic agent

Acta Pharmacol Sin. 2011 Mar;32(3):311-20. doi: 10.1038/aps.2010.207. Epub 2011 Jan 24.

Abstract

Aim: To examine the electrophysiological effects of sophocarpine on action potentials (AP) and ionic currents of cardiac myocytes and to compare some of these effects with those of amiodarone.

Methods: Langendorff perfusion set-up was used in isolated guinea pig heart, and responses to sophocarpine were monitored using electrocardiograph. Conventional microelectrode, voltage clamp technique and perforated patch were employed to record fast response AP (fAP), slow response AP (sAP) and ionic currents in guinea pig papillary muscle or rabbit sinus node cells.

Results: Tachyarrhythmia produced by isoprenaline (15 μmol/L) could be reversed by sophocarpine (300 μmol/L). Sophocarpine (10 μmol/L) decreased the amplitude by 4.0%, maximal depolarization velocity (V(max)) of the fAP by 24.4%, and Na(+) current (I(Na)) by 18.0%, while it prolonged the effective refractory period (ERP) by 21.1%. The same concentration of sophocarpine could also decrease the amplitude and V(max) of the sAP, by 26.8% and 25.7%, respectively, and attenuated the Ca(2+) current (I(CaL)) and the K(+) tail current substantially. Comparison of sophocarpine with amiodarone demonstrated that both prolonged the duration and the ERP of fAP and sAP, both decreased the amplitude and V(max) of the fAP and sAP, and both slowed the automatic heart rate.

Conclusion: Sophocarpine could reverse isoprenaline-induced arrhythmia and inhibit I(Na), I(CaL), and I(Kr) currents. The electrophysiological effects of sophocarpine are similar to those of amiodarone, which might be regarded as a prospective antiarrhythmic agent.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Alkaloids / pharmacology*
  • Alkaloids / therapeutic use
  • Amiodarone / pharmacology
  • Amiodarone / therapeutic use
  • Animals
  • Anti-Arrhythmia Agents / pharmacology*
  • Anti-Arrhythmia Agents / therapeutic use
  • Cells, Cultured
  • Electrophysiological Phenomena*
  • Female
  • Guinea Pigs
  • Heart / drug effects*
  • Heart / physiology
  • Male
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / physiology
  • Papillary Muscles / drug effects
  • Papillary Muscles / physiology
  • Patch-Clamp Techniques
  • Rabbits
  • Sodium / metabolism
  • Tachycardia / drug therapy*
  • Tachycardia / physiopathology

Substances

  • Alkaloids
  • Anti-Arrhythmia Agents
  • sophocarpine
  • Sodium
  • Amiodarone