miR-19b调控斑马鱼左心室动作电位
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miR-19b Regulates Ventricular Action Potential Duration in Zebrafsh
文献摘要
由室性心律失常引起的心脏性猝死通常由动作电位时程（APD）延长引起，是心力衰竭（HF）中常见的死亡类型。调节基因表达的微小 RNA，非编码RNA在HF期间经常失调，提示可能参与伴随HF进展的电重构过程。在这里，我们认为miR-19b心脏功能的重要调节因子。缺乏miR-19b的斑马鱼出现了严重的心动过缓和心肌收缩功能减弱。缺乏miR-19b的斑马鱼对房室传导阻滞的敏感性增加，这是斑马鱼长QT综合征的一个特征。心肌全细胞膜片钳实验显示，缺乏miR-19b的斑马鱼表现出显著延长的由复极受损引起的心室APD。我们发现，miR-19b直接和间接调节心脏离子通道的关键调节亚基的表达，从而调节AP持续时间和形状。有趣的是，miR-19b敲除介导的APD延长可逆转基因诱导的短QT表型。因此，miR-19b可能是心脏电活动的一个重要调节因素，我们的工作确立了miR-19b作为人类长QT综合征的潜在致病因素。
原始文献摘要
Benz A, Kossack M, Auth D, et al. miR-19b Regulates Ventricular Action Potential Duration in Zebrafish[J]. Scientific Reports, 2016, 6:36033.
Abstract
Sudden cardiac death due to ventricular arrhythmias often caused by action potential duration (APD) prolongation is a common mode of death in heart failure (HF). microRNAs, noncoding RNAs that fine tune gene expression, are frequently dysregulated during HF, suggesting a potential involvement in the electrical remodeling process accompanying HF progression. Here, we identified miR-19b as an important regulator of heart function. Zebrafish lacking miR-19b developed severe bradycardia and reduced cardiac contractility. miR-19b deficient fish displayed increased sensitivity to AV-block, a characteristic feature of long QT syndrome in zebrafish. Patch clamp experiments from whole hearts showed that miR-19b deficient zebrafish exhibit significantly prolonged ventricular APD caused by impaired repolarization. We found that miR-19b directly and indirectly regulates the expression of crucial modulatory subunits of cardiac ion channels, and thereby modulates AP duration and shape. Interestingly, miR-19b knockdown mediated APD prolongation can rescue a genetically induced short QT phenotype. Thus, miR-19b might represent a crucial modifier of the cardiac electrical activity, and our work establishes miR-19b as a potential candidate for human long QT syndrome.
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