%0 Generic
%A Benz, Alexander
%D 2016
%F heidok:21404
%R 10.11588/heidok.00021404
%T miR-19b - ein essentieller Regulator der Länge und Form  des ventrikulären Aktionspotentials im Zebrafisch
%U https://archiv.ub.uni-heidelberg.de/volltextserver/21404/
%X Sudden cardiac death (SCD) is a common mode of death in heart failure (HF) and results  from prolonged action potential duration (APD) and ventricular arrhythmias. During the  pathogenesis and progression of HF, a myriad number of signaling pathways are altered,  including microRNAs. microRNAs are small noncoding RNAs that fine-tune gene expression  by translational repression or transcript destabilization. Interestingly, microRNAs are  dysregulated during HF, suggesting a potential involvement in the development and  progression of the disease. Here, miR-19 was identified as an important regulator of heart  function. Zebrafish lacking miR-19 developed severe bradycardia and reduced cardiac  contractility. While mammals express two isoforms of miR-19, the zebrafish genome encodes  for four members (19a-d). The reduction of miR-19b specifically was found to be sufficient to  reduce heart rate by 30 % and to induce heart failure. Patch-clamp experiments from whole  hearts showed that miR-19b deficient zebrafish exhibit significantly prolonged ventricular  APD caused by impaired repolarization. Additionally these fish show increased sensitivity to  an AV-Block, which is a characteristic feature of long QT-Syndrome in zebrafish. qRT-PCR  revealed that miR-19b directly and indirectly regulates the expression of cardiac ion channels  and thereby modulates APD and shape. This study describes miR-19b as an essential  regulator of electrical activity of the heart and identifies it as a potential candidate gene  causative for human long QT syndrome.