Effects of Autoantibodies against M2 Muscarinic Acetylcholine Receptors on Rabbit Atria in vivo

被引：29

作者：

Hong, Chang Ming ^{[1
]}

Zheng, Qiang Sun ^{[1
]}

Liu, Xiong Tao ^{[1
]}

Shang, Fu Jun ^{[1
]}

Wang, Hong Tao ^{[1
]}

Jiang, Wen Rui ^{[1
]}

机构：

[1] Fourth Mil Med Univ, Affiliated Hosp 2, Dept Cardiol, Xian 710038, Shaanxi, Peoples R China

来源：

CARDIOLOGY | 2009年 / 112卷 / 03期

关键词：

M2 muscarinic acetylcholine receptor; Dilated cardiomyopathy; Atrial fibrillation; Atrial fibrosis; Muscarinic-gated atrial potassium channel; 2ND EXTRACELLULAR LOOP; HEART-FAILURE; DILATED CARDIOMYOPATHY; FIBRILLATION; EXPRESSION; ANTIBODIES; CONDUCTION; DISEASE;

D O I：

10.1159/000149152

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Evidence has shown that autoantibodies against M2 muscarinic acetylcholine receptors may play a role in the development of atrial fibrillation. The goal of this study was to evaluate the effects of anti-M2 receptor autoantibodies on rabbit atria in vivo. Methods: Rabbits were immunized monthly with a synthetic peptide corresponding to the M2 receptor. The atrial electrophysiology of the isolated perfused rabbit hearts was studied. Western blots and RTPCR were performed to determine the expression of the atrial muscarinic receptor and the acetylcholine-activated potassium channel. Atrial tissue was stained with Masson's trichrome stain for fibrosis detection. Results: Autoantibodies were persistently detected in immunized rabbits. M2 rabbits showed a significantly shorter atrial effective refractory period and a longer intra-atrial activation time than control rabbits. Electrical stimuli induced a significantly larger number of repetitive atrial responses in M2 rabbits. The protein levels of the M2 receptor and GIRK4 were upregulated in M2 rabbits. The mRNA levels of GIRK1 and GIRK4 were also up-regulated. Histological examination revealed significantly increased diffuse fibrotic deposition in M2 rabbit atria compared with control rabbits. Conclusion: The M2 receptor autoantibody-positive rabbits showed altered atrial electrophysiology, overexpression of the M2 receptor-I-K,(ACh) pathway and atrial fibrosis, which indicates that the auto-antibodies against M2 receptors may participate in the induction and perpetuation of atrial fibrillation. Copyright (c) 2008 S. Karger AG, Basel

引用

页码：180 / 187

页数：8

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