1. Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China
2. Department of Cardiology, the Second Affiliated Hospital of Harbin Medical University
3. Department of Pathophysiology, Harbin Medical University, Harbin, China
# These authors contributed equally to this study.
Aim: To elucidate the protective effects of Matrine on atrial fibrillation (AF) induced by electric pacing in mice and underlying molecular and ion channel mechanisms.
Methods: AF was introduced by electric pacing in mice and the incidence and duration of AF were evaluated. Functional expression of M3 receptor (M3-R) and Cav1.2 were explored by western and Real-time PCR, action potential (AP) and the density of (IKM3) L-type calcium channel (ICa-L) were both recorded using whole-cell patch in isolated atrial cardiomyocytes.
Results: In control group, incidence and duration of AF induced by electric pacing were 50 ± 17% and 3.68 ± 1.84 s, respectively; after application of carbachol 50 µg/kg both incidence and duration of AF were significantly increased to 86 ± 24% and 65.2 ± 29.0 s. Compared with control group, pretreatment of Matrine for 15 days significantly reduced AF incidence and duration in dose-dependent manner. Atrial membrane-protein expression of M3-R was decreased and membrane Cav1.2 expression was up-regulated. In single Matrine-treated atrial cardiomyocyte the density of IKM3 was significantly decreased by 39% as well compared with control group, P < 0.05, whereas, ICa-L density of atrium was increased by 40%.
Conclusion: These data demonstrated at the first time that the anti-AF effects of Matrine may due, at least in part, to down-regulation of IKM3 density and M3-R expression and up-regulation of ICa-L density and α1C/Cav1.2 expression.
Keywords: atrial fibrillation, M3 receptor, L-type calcium channel, potassium channel, Matrine