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 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.
Department of Medicine III, Cardiology, Angiology and Pneumology, University Hospital of Heidelberg, 69120 Heidelberg, Germany.|DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany.
Alexander
A
Benz
Department of Medicine III, Cardiology, Angiology and Pneumology, University Hospital of Heidelberg, 69120 Heidelberg, Germany.|DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany.
Mandy
M
Kossack
Department of Medicine III, Cardiology, Angiology and Pneumology, University Hospital of Heidelberg, 69120 Heidelberg, Germany.
Dominik
D
Auth
Department of Medicine III, Cardiology, Angiology and Pneumology, University Hospital of Heidelberg, 69120 Heidelberg, Germany.|DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany.
Claudia
C
Seyler
Department of Medicine III, Cardiology, Angiology and Pneumology, University Hospital of Heidelberg, 69120 Heidelberg, Germany.|DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany.
Edgar
E
Zitron
Department of Medicine III, Cardiology, Angiology and Pneumology, University Hospital of Heidelberg, 69120 Heidelberg, Germany.|DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany.
Lonny
L
Juergensen
Department of Medicine III, Cardiology, Angiology and Pneumology, University Hospital of Heidelberg, 69120 Heidelberg, Germany.|DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany.
Hugo A
HA
Katus
Department of Medicine III, Cardiology, Angiology and Pneumology, University Hospital of Heidelberg, 69120 Heidelberg, Germany.|DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany.
David
D
Hassel
D000200:Action Potentials / Q000235:genetics*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics* / Q000503:physiopathology; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D008133:Long QT Syndrome / Q000235:genetics* / Q000503:physiopathology; D035683:MicroRNAs / Q000235:genetics*; D009200:Myocardial Contraction / Q000235:genetics; D015221:Potassium Channels / Q000235:genetics; D015027:Zebrafish / Q000235:genetics / Q000502:physiology
C000601318:MIRN19 microRNA, zebrafish; D035683:MicroRNAs; D015221:Potassium Channels