Local Onset of Voltage and Calcium Alternans in the Heart

Author(s):  
Stephen D. McIntyre ◽  
Yoichiro Mori ◽  
Elena G. Tolkacheva

A beat-to-beat variation in cardiac action potential durations (APD) is a phenomenon known as electrical alternans. Alternans desynchronizes depolarization, increases dispersion of refractoriness and creates a substrate for ventricular fibrillation. In the heart, APD alternans can be accompanied by alternans in intracellular calcium ([Ca2+]i) transients. Recently, we demonstrated experimentally that the onset of APD alternans in the heart is a local phenomenon that undergoes complex spatiotemporal dynamics as pacing rate increases. Moreover, the local onset of APD alternans can be predicted by measuring the restitution properties of periodically paced cardiac tissue. The purpose of this research is to investigate the interplay between local onsets of APD and [Ca2+]i alternans using 2D simulation of action potential model of cardiac myocytes.

2012 ◽  
Vol 66 (2) ◽  
pp. 171
Author(s):  
Giovanni Y. Di Veroli ◽  
Mark Davies ◽  
Chris E. Pollard ◽  
Jean-Pierre Valentin ◽  
Henggui Zhang ◽  
...  

2006 ◽  
Vol 20 (5) ◽  
Author(s):  
Ching‐Hsing Luo ◽  
Po‐Yuan Chen ◽  
Chun‐Hao Teng ◽  
Ching‐Ting Lee ◽  
Ruey‐Jen Sung

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.


Author(s):  
Kenneth T. MacLeod ◽  
Steven B. Marston ◽  
Philip A. Poole-Wilson ◽  
Nicholas J. Severs ◽  
Peter H. Sugden

Cardiac myocytes are the contractile cells of the heart and constitute the bulk of heart mass. There are differences between the myocytes of the ventricles, the atria, and the conduction system: ventricular myocytes are elongated cells and packed with myofibrils (the contractile apparatus) and mitochondria (for ATP production)....


2010 ◽  
pp. 2604-2618 ◽  
Author(s):  
Kenneth T. MacLeod ◽  
Steven B. Marston ◽  
Philip A. Poole-Wilson ◽  
Nicholas J. Severs ◽  
Peter H. Sugden

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