Matrine inhibits pacing induced atrial fibrillation by modulating I(KM3) and I(Ca-L).
OBJECTIVE
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 M(3) receptor (M(3)-R) and Cav1.2 were explored by western and Real-time PCR, action potential (AP) and the density of (I(KM3)) L-type calcium channel (I(Ca-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 M(3)-R was decreased and membrane Cav1.2 expression was up-regulated. In single Matrine-treated atrial cardiomyocyte the density of I(KM3) was significantly decreased by 39% as well compared with control group, P < 0.05, whereas, I(Ca-L) density of atrium was increased by 40%.


CONCLUSIONS
These data demonstrated at the first time that the anti-AF effects of Matrine may due, at least in part, to down-regulation of I(KM3) density and M(3)-R expression and up-regulation of I(Ca-L )density and α1C/Cav1.2 expression.
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, PR China.
Yuhong
Y
Zhou
Wei
W
Xu
Ruyi
R
Han
Jiaying
J
Zhou
Zhenwei
Z
Pan
Huo
H
Rong
Junnan
J
Li
Changqing
C
Xu
Guofen
G
Qiao
Yanjie
Y
Lu
D000200:Action Potentials; D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001281:Atrial Fibrillation / Q000517:prevention & control*; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D002304:Cardiac Pacing, Artificial; D006325:Heart Atria / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011807:Quinolizines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D043587:Receptor, Muscarinic M3 / Q000378:metabolism; D000093842:Matrines
D000470:Alkaloids; D020746:Calcium Channels, L-Type; D020011:Protective Agents; D011807:Quinolizines; D043587:Receptor, Muscarinic M3; D002118:Calcium; D000093842:Matrines