MiR-19b regulates ventricular action potential duration in Zebrafish
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...
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| Main Authors: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
02 November 2016
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| In: |
Scientific reports
Year: 2016, Volume: 6 |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep36033 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1038/srep36033 Verlag, Volltext: https://www.nature.com/articles/srep36033 
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| Author Notes: | Alexander Benz, Mandy Kossack, Dominik Auth, Claudia Seyler, Edgar Zitron, Lonny Juergensen, Hugo A. Katus & David Hassel |
| Summary: | 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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| Item Description: | Gesehen am 18.04.2019 |
| Physical Description: | Online Resource |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep36033 |