Matrine inhibits pacing induced atrial fibrillation by modulating I(KM3) and I(Ca-L)

Int J Biol Sci. 2012;8(1):150-8. doi: 10.7150/ijbs.8.150. Epub 2011 Dec 9.

Abstract

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 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%.

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 I(KM3) density and M(3)-R expression and up-regulation of I(Ca-L )density and α1C/Cav1.2 expression.

Keywords: L-type calcium channel; M3 receptor; Matrine; atrial fibrillation; potassium channel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Alkaloids / chemistry
  • Alkaloids / pharmacology*
  • Alkaloids / therapeutic use
  • Animals
  • Atrial Fibrillation / prevention & control*
  • Calcium / metabolism
  • Calcium Channels, L-Type / drug effects*
  • Cardiac Pacing, Artificial*
  • Heart Atria / metabolism
  • Heart Atria / physiopathology
  • Matrines
  • Mice
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Protective Agents / chemistry
  • Protective Agents / pharmacology*
  • Protective Agents / therapeutic use
  • Quinolizines / chemistry
  • Quinolizines / pharmacology*
  • Quinolizines / therapeutic use
  • Receptor, Muscarinic M3 / metabolism

Substances

  • Alkaloids
  • Calcium Channels, L-Type
  • Protective Agents
  • Quinolizines
  • Receptor, Muscarinic M3
  • Calcium
  • Matrines