心脏电流表达的反改造:一种用于控制复极化储备的新潜在机制
Ling Xiao1, Jiening Xiao, Xiaobin Luo
1Department of Medicine, Montreal Heart Institute and Université de Montréal, Quebec, Canada.
Circulation
|August 20, 2008
概括
持续抑制心肌细胞中的快速延迟校正剂电流 (I(Kr)) 通过转录后调节增加了缓慢延迟校正剂电流 (I(Ks)). 这表明microRNA变化影响心脏再极化储备.
科学领域:
- 心血管生理学心血管生理学
- 分子心脏病学分子心脏病学
- 离子通道生物学 离子通道生物学
背景情况:
- 抑制单个K(+) 电流导致其他K(+) 电流的补偿增长,保持动作潜力的持续时间 (再极化储备).
- 持续的K(+) 通道抑制对离子电流表达 (重塑) 的影响仍然在很大程度上未被探索.
- 这项研究研究了慢性K(+) 电流抑制对心脏离子电流表达的影响.
研究的目的:
- 要确定是否持续抑制快速延迟校正器K(+) 电流 (I(Kr)) 诱导其他心脏离子电流的重塑.
- 阐明任何观察到的离子电流表达的变化背后的机制.
- 评估这些变化对再极化储备的影响.
主要方法:
- 成年犬的左心室心肌细胞被培养,并与选择性I(Kr) 阻断剂多菲提利德 (dofetilide) 或没有它一起进行24小时的节奏.
- 评估了行动潜力的持续时间和再极化储备.
- 量化了离子电流密度 (I ((Kr),I ((Ks),I ((to),I ((K1),I ((CaL)),mRNA和KvLQT1/minK的蛋白质表达,以及微RNA水平 (miR-133a/b).
主要成果:
- 持续的I(Kr) 封锁缩短了行动潜力的持续时间,并增加了再极化储备.
- 观察到缓慢延迟校正器K ((+) 电流 (I ((Ks)) 密度的显著增加,而其他测量电流没有变化.
- 在mRNA没有变化的情况下,KvLQT1/minK蛋白水平增加,这表明后转录调节,可能涉及减少miR-133a/b表达.
结论:
- 持续的I ((Kr) 减少可以通过转录后机制导致补偿I ((Ks) 上调,可能涉及微RNA介导调节.
- 这些发现突出显示了离子通道表达中的反控制系统,该系统调节心脏再极化储备.
- 离子通道表达的这种重塑可能对心脏电生理学和心律失常产生影响.
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