scholarly journals MicroRNA-365 regulates human cardiac action potential duration

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Dena Esfandyari ◽  
Bio Maria Ghéo Idrissou ◽  
Konstantin Hennis ◽  
Petros Avramopoulos ◽  
Anne Dueck ◽  
...  

AbstractAbnormalities of ventricular action potential cause malignant cardiac arrhythmias and sudden cardiac death. Here, we aim to identify microRNAs that regulate the human cardiac action potential and ask whether their manipulation allows for therapeutic modulation of action potential abnormalities. Quantitative analysis of the microRNA targetomes in human cardiac myocytes identifies miR-365 as a primary microRNA to regulate repolarizing ion channels. Action potential recordings in patient-specific induced pluripotent stem cell-derived cardiac myocytes show that elevation of miR-365 significantly prolongs action potential duration in myocytes derived from a Short-QT syndrome patient, whereas specific inhibition of miR-365 normalizes pathologically prolonged action potential in Long-QT syndrome myocytes. Transcriptome analyses in these cells at bulk and single-cell level corroborate the key cardiac repolarizing channels as direct targets of miR-365, together with functionally synergistic regulation of additional action potential-regulating genes by this microRNA. Whole-cell patch-clamp experiments confirm miR-365-dependent regulation of repolarizing ionic current Iks. Finally, refractory period measurements in human myocardial slices substantiate the regulatory effect of miR-365 on action potential in adult human myocardial tissue. Our results delineate miR-365 to regulate human cardiac action potential duration by targeting key factors of cardiac repolarization.

2017 ◽  
Vol 95 (10) ◽  
pp. 1230-1235 ◽  
Author(s):  
Péter P. Nánási ◽  
János Magyar ◽  
András Varró ◽  
Balázs Ördög

Beat-to-beat variability of cardiac action potential duration (short-term variability, SV) is a common feature of various cardiac preparations, including the human heart. Although it is believed to be one of the best arrhythmia predictors, the underlying mechanisms are not fully understood at present. The magnitude of SV is basically determined by the intensity of cell-to-cell coupling in multicellular preparations and by the duration of the action potential (APD). To compensate for the APD-dependent nature of SV, the concept of relative SV (RSV) has been introduced by normalizing the changes of SV to the concomitant changes in APD. RSV is reduced by ICa, IKr, and IKs while increased by INa, suggesting that ion currents involved in the negative feedback regulation of APD tend to keep RSV at a low level. RSV is also influenced by intracellular calcium concentration and tissue redox potential. The clinical implications of APD variability is discussed in detail.


1983 ◽  
Vol 345 (1) ◽  
pp. 75-85 ◽  
Author(s):  
A J Drake-Holland ◽  
M I Noble ◽  
M Pieterse ◽  
V J Schouten ◽  
W A Seed ◽  
...  

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