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 (Vmax) of the fAP by 24.4%, and Na+ current (INa) 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 Vmax of the sAP, by 26.8% and 25.7%, respectively, and attenuated the Ca2+ current (ICaL) 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 Vmax of the fAP and sAP, and both slowed the automatic heart rate.
Conclusion:
Sophocarpine could reverse isoprenaline-induced arrhythmia and inhibit INa, ICaL, and IKr currents. The electrophysiological effects of sophocarpine are similar to those of amiodarone, which might be regarded as a prospective antiarrhythmic agent.
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Acknowledgements
This work was supported by the Science Foundation of the Shanghai Science Committee Foundation (No 06JC14045) and the Science Foundation of Shanghai Health Bureau (No 2009045).
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Yang, Zf., Li, Cz., Wang, W. et al. Electrophysiological mechanisms of sophocarpine as a potential antiarrhythmic agent. Acta Pharmacol Sin 32, 311–320 (2011). https://doi.org/10.1038/aps.2010.207
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DOI: https://doi.org/10.1038/aps.2010.207
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