Paper
N-Methylberbamine extends the action potential of the cardiac ventricular myocytes of rabbits through inhibiting an outward rectifying current
Published 2018 ยท Shi Zhou, Xiao-dong Sun, Sun Xuanxuan
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Abstract
Background Accumulated data show that N-methylberbamine (N-MB), a berberine derivative, has marked antiarrhythmic effect through influencing the electric activities of cardiac ventricular myocytes. However, the underlying mechanisms are still ill-defined. In this study, the effects of N-MB on the action potential, L-type calcium current and outward rectifying current in the cardiac ventricular myocytes of rabbits were investigated to deduce its mechanism of anti-arrythmias. Methods The action potential and transmembrane ionic currents were elicited from the single rabbit ventricular myocytes under the whole-cell current/voltage clamp condition. And the binding of N-MB to Cav1.2 calcium channel or Kv11.1 potassium channel was evaluated by molecular docking technique. Results Following a 5 min perfusion with 1 micromolar N-MB containing Tyrode solution, the duration of action potentials (APD20, APD50 and APD90) were dramatically extended and the amplitude of action potential (APA) was partially reduced. N-MB decreased the amplitude of each peak ICa. Meanwhile, neither V1/2 nor K was altered significantly. In addition, N-MB not only abolished the feature of Itail completely, but also reduced its amplitude to zero level from control values at different membrane potentials from -20 mV to +50 mV. The results of molecular docking showed that N-MB could bind to the IV domain of Cav1.2 channel or Kv11.1 channel with higher binding scores than there corresponding inhibitors (verapamil or dofetilide), indicating that N-MB could bind to these two channels in a stable conformation. Conclusion N-MB inhibited the slow inward and outward rectifying currents, but meantime dramatically extended the action potential durations, indicating that the N-MB may perform its antiarrythmic efect through blocking both calcium and potassium channels.
In Vitro StudyN-methylberbamine extends action potential durations in rabbit cardiac ventricular myocytes by inhibiting slow inward and outward rectifying currents, suggesting its antiarrhythmic effect through blocking both calcium and potassium channels.
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