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A potent antiarrhythmic drug N-methyl berbamine extends the action potential through inhibiting both calcium and potassium currents
- Source :
- Journal of Pharmacological Sciences, Vol 142, Iss 4, Pp 131-139 (2020)
- Publication Year :
- 2019
-
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 CaV1.2 Ca2+ and KV11.1 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 hCaV1.2 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 CaV1.2 and KV11.1 channels. Following a perfusion with N-MB, the durations of action potentials (APD20, APD50 and APD90) were extended, and the outward tail current, Itail, as well as the hERG current, IhERG, 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, ICaL, as well as the CaV1.2 current, ICaV1.2; 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. Keywords: N-methyl berbamine, Action potential, Ca2+ current, K+ current, Multitarget
- Subjects :
- 0301 basic medicine
Potassium
hERG
chemistry.chemical_element
Action Potentials
Calcium
Pharmacology
Berbamine
Benzylisoquinolines
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Berberine
Potassium Channel Blockers
biology
Chinese hamster ovary cell
lcsh:RM1-950
Transfection
Calcium Channel Blockers
lcsh:Therapeutics. Pharmacology
030104 developmental biology
chemistry
biology.protein
Molecular Medicine
Perfusion
Anti-Arrhythmia Agents
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 13478648
- Volume :
- 142
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Journal of pharmacological sciences
- Accession number :
- edsair.doi.dedup.....2d1a3e0ce855911256b86189d4c92076