增强的sarcoplasmic网膜Ca2+泄漏和增加的Na+-Ca2+交换器功能是慢性心房动患者延迟脱极化后的基础
Niels Voigt1, Na Li, Qiongling Wang
1Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Germany.
Circulation
|March 30, 2012
概括
在心房患者中,由Ca2+/卡尔莫杜林依赖蛋白激酶-II (CaMKII) 和瑞诺丁受体 (RyR2) 驱动的质网膜Ca2+) 泄漏增加,促进危险的心律.
科学领域:
- 心脏病学 心脏病学
- 分子生物学分子生物学
- 电子生理学 电子生理学
背景情况:
- 由Na(+) -Ca(2+) -交换电流 (I(NCX)) 介导的延迟后去极化 (DADs) 可以引发心房动 (AF).
- 在AF患者中DADs背后的机制尚不清楚.
研究的目的:
- 在慢性AF (cAF) 患者中研究DADs的机制.
- 在cAF中识别了sarcoplasmic网膜 (SR) Ca(2+) 处理和RyR2功能中的分子变化.
主要方法:
- 通过Western blot,补丁和Fluo-3成像,分析了对照和cAF患者的右心房样本.
- 测量SR Ca ((2+) 泄漏,RyR2开放概率和蛋白质酸化.
- 药理上抑制CaMKII和蛋白激酶A的作用.
- 在具有改变RyR2酸化的实验小鼠中进行的研究.
主要成果:
- cAF患者表现出显著更高的透析式SR Ca(2+) 泄漏和增强的RyR2开放概率.
- 在cAF中观察到CaMKII的表达和活性增加以及 RyR2在特定部位的酸化.
- 抑制CaMKII可以减少SR Ca2+) 泄漏和自发Ca2+) 释放事件.
- 在cAF中,I(NCX) 的调节升高,并且扩张性[Ca(2+) ](i) 电压合增益升高.
结论:
- 通过CaMKII-超酸化RyR2增强的SR Ca(2+) 泄漏是cAF中DADs的一个关键机制.
- 增加的I (NCX) 和增加的透静[Ca (NC2+) ] (i) 电压合增益有助于AF促进.
相关概念视频
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