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ZFIN ID: ZDB-PUB-161103-6
miR-19b Regulates Ventricular Action Potential Duration in Zebrafish
Benz, A., Kossack, M., Auth, D., Seyler, C., Zitron, E., Juergensen, L., Katus, H.A., Hassel, D.
Date: 2016
Source: Scientific Reports 6: 36033 (Journal)
Registered Authors: Hassel, David
Keywords: Cardiovascular biology, Molecular biology
MeSH Terms:
  • Action Potentials/genetics*
  • Animals
  • Arrhythmias, Cardiac/genetics*
  • Arrhythmias, Cardiac/physiopathology
  • Disease Models, Animal
  • Heart Ventricles/physiopathology
  • Humans
  • Long QT Syndrome/genetics*
  • Long QT Syndrome/physiopathology
  • MicroRNAs/genetics*
  • Myocardial Contraction/genetics
  • Potassium Channels/genetics
  • Zebrafish/genetics
  • Zebrafish/physiology
PubMed: 27805004 Full text @ Sci. Rep.
FIGURES
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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