A potent antiarrhythmic drug N-methyl berbamine extends the action potential through inhibiting both calcium and potassium currents

Abstract

N-methyl berbamine (N-MB) is a berberine derivative. Its analogue berbamine has been reported to have remarkable antiarrhythmic and ischemic protective effects. However, the pharmacological effects of N-MB are ill-defined. In this study, molecular docking was used to evaluate the binding of N-MB to Ca_V1.2 Ca²⁺ and K_V11.1 K⁺ channels, and the effects of N-MB on action potential and ionic currents were observed in the ventricular myocytes of rabbits, HEK293 cells stably transfected with the hCa_V1.2 gene and CHO cells stably transfected with hERG (human ether-a-go-go related gene). The results showed that N-MB was able to bind to both Ca_V1.2 and K_V11.1 channels. Following a perfusion with N-MB, the durations of action potentials (APD₂₀, APD₅₀ and APD₉₀) were extended, and the outward tail current, I_tail, as well as the hERG current, I_hERG, were inhibited, while the amplitude of action potential (APA) was only slightly reduced. N-MB also decreased the peak amplitude of the L-type Ca²⁺ channel current, I_CaL, as well as the Ca_V1.2 current, I_CaV1.2; this may limit the prolongation of APD. In conclusion, N-MB is a potent and natural antiarrhythmic multitarget drug that may elicit its antiarrhythmic effect through blocking both Ca²⁺ and K⁺ channel currents.