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人类心房颤动中钙通道α1C亚基突变的缺失

Absence of calcium channel alpha1C-subunit mutation in human atrial fibrillation.

作者信息

Soon Jia-Lin, Ping Liao, Chua Yeow-Leng, Soong Tuck-Wah, Sin Kenny Yoong-Kong

机构信息

Department of Cardiothoracic Surgery, National Heart Center, National University of Singapore, Singapore.

出版信息

Asian Cardiovasc Thorac Ann. 2010 Aug;18(4):349-53. doi: 10.1177/0218492310375749.

DOI:10.1177/0218492310375749
PMID:20719785
Abstract

L-type voltage-gated calcium channel mutation or phenotypical variation resulting from alternative splicing has been associated with sudden arrhythmogenic death and heart failure. Changes in calcium current density, protein and mRNA expression have been associated with atrial fibrillation. We studied human atrium harvested from 16 cardiac surgery patients (coronary bypass and/or valve procedures) for mutation of Ca(v)1.2 alpha(1C) (the main pore-forming subunit of L-type voltage-gated calcium channel) for an association with atrial fibrillation. Seven patients had persistent atrial fibrillation and one was resuscitated from ventricular arrhythmia. Clinical data were collected and prospectively updated for the development of arrhythmia. Four (25%) patients had new-onset postoperative paroxysmal atrial fibrillation. DNA from all atrial specimens was amplified, extracted, and sequenced. The alpha(1C)-subunit mutation was absent in all specimens obtained from all patients, regardless of heart rhythm. This suggests that atrial fibrillation is not associated with loss-of-function mutation of the main pore-forming subunit of the L-type voltage-gated calcium channel.

摘要

L型电压门控钙通道突变或因可变剪接导致的表型变异与致心律失常性猝死及心力衰竭相关。钙电流密度、蛋白质及mRNA表达的改变与心房颤动有关。我们研究了从16例心脏手术患者(冠状动脉搭桥和/或瓣膜手术)获取的人心房组织,检测Ca(v)1.2 α(1C)(L型电压门控钙通道的主要孔形成亚基)的突变情况,以探讨其与心房颤动的关联。7例患者患有持续性心房颤动,1例从室性心律失常中复苏。收集临床数据并对心律失常的发生进行前瞻性更新。4例(25%)患者术后出现新发阵发性心房颤动。对所有心房标本的DNA进行扩增、提取和测序。所有患者的所有标本中均未检测到α(1C)亚基突变,无论其心律如何。这表明心房颤动与L型电压门控钙通道主要孔形成亚基的功能丧失突变无关。

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Am J Transl Res. 2017 Apr 15;9(4):1822-1833. eCollection 2017.