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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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Hauptverfasser: Benz, Alexander (Verfasst von) , Kossack, Mandy (Verfasst von) , Auth, Dominik (Verfasst von) , Seyler, Claudia (Verfasst von) , Zitron, Edgar (Verfasst von) , Jürgensen, Lonny (Verfasst von) , Katus, Hugo (Verfasst von) , Hassel, David (Verfasst von)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 02 November 2016
In: Scientific reports
Year: 2016, Jahrgang: 6
ISSN:2045-2322
DOI:10.1038/srep36033
Online-Zugang:Verlag, Volltext: https://doi.org/10.1038/srep36033
Verlag, Volltext: https://www.nature.com/articles/srep36033
Volltext
Verfasserangaben:Alexander Benz, Mandy Kossack, Dominik Auth, Claudia Seyler, Edgar Zitron, Lonny Juergensen, Hugo A. Katus & David Hassel
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Zusammenfassung: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.
Beschreibung:Gesehen am 18.04.2019
Beschreibung:Online Resource
ISSN:2045-2322
DOI:10.1038/srep36033

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