MiR-19b regulates ventricular action potential duration in Zebrafish

• Verfasst von: Benz, Alexander [VerfasserIn]
• Verfasst von: Kossack, Mandy [VerfasserIn]
• Verfasst von: Auth, Dominik [VerfasserIn]
• Verfasst von: Seyler, Claudia [VerfasserIn]
• Verfasst von: Zitron, Edgar [VerfasserIn]
• Verfasst von: Jürgensen, Lonny [VerfasserIn]
• Verfasst von: Katus, Hugo [VerfasserIn]
• Verfasst von: Hassel, David [VerfasserIn]
• Titel: MiR-19b regulates ventricular action potential duration in Zebrafish
• Verf.angabe: Alexander Benz, Mandy Kossack, Dominik Auth, Claudia Seyler, Edgar Zitron, Lonny Juergensen, Hugo A. Katus & David Hassel
• E-Jahr: 2016
• Jahr: 02 November 2016
• Umfang: 11 S.
• Fussnoten: Gesehen am 18.04.2019
• Titel Quelle: Enthalten in: Scientific reports
• Ort Quelle: [London] : Macmillan Publishers Limited, part of Springer Nature, 2011
• Jahr Quelle: 2016
• Band/Heft Quelle: 6(2016) Artikel-Nummer 36033, 11 Seiten
• ISSN Quelle: 2045-2322
• DOI: doi:10.1038/srep36033
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1663435073

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.