Effect of Percentage Reduction in Action Potential Duration of M-cells on Re-entry in Short QT Syndrome

2020 ◽  
Author(s):  
Ponnuraj Kirthi Priya ◽  
Srinivasan Jayaraman
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
M Cells ◽  
Percentage Reduction ◽  
Short Qt Syndrome ◽  
Qt Syndrome

Modelling of short QT syndrome in a heterogeneous model of the human ventricular wall

EP Europace ◽  
2005 ◽  
Vol 7 (s2) ◽  
pp. S105-S117 ◽  
Author(s):  
Daniel L. Weiss ◽  
Gunnar Seemann ◽  
Frank B. Sachse ◽  
Olaf Dössel
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Short Qt Syndrome ◽  
Detailed Model ◽  
Heterogeneous Model ◽  
T Wave ◽  
Dispersion Of Repolarization ◽  
Cellular Environment ◽  
Qt Syndrome ◽  
Experimental Findings

Abstract Aims A percentage of sudden cardiac death events occur in individuals with structurally normal hearts due to an abnormality in the ion channel activity. While the majority of these hereditary syndromes are well-established, little is known about the significance of the short QT syndrome. Methods This study is based on discovered insights into the molecular basis of the originally described form of this disease. A biophysically detailed model of cellular electrophysiology was adapted to emulate the behaviour of cells affected by the short QT syndrome. Simulations were performed in single cell and homogeneous as well as heterogeneous anisotropic multi-cellular environment describing the human left ventricle. Results The short QT mutation increased the activity of the repolarizing outward potassium current IKr. The heterogeneous abbreviation of the action potential duration decreased the dispersion of repolarization in heterogeneous tissue. Repolarization was homogenized and the final repolarization was shifted to epicardial sites. The transmural ECG showed a shortened QT interval and a T wave with reduced amplitude. Conclusion The altered characteristics of the mutant IKr current were consistent with experimental findings. The heterogeneous reduction of the action potential duration and the reduced T wave amplitude need to be verified by measurements.

Bupivacaine Destabilizes Action Potential Duration in Cellular and Computational Models of Long QT Syndrome 1

2011 ◽  
Vol 113 (6) ◽  
pp. 1365-1373 ◽  
Author(s):  
Alexander P. Schwoerer ◽  
Roman Zenouzi ◽  
Heimo Ehmke ◽  
Patrick Friederich
Keyword(s):  
Action Potential ◽  
Long Qt Syndrome ◽  
Action Potential Duration ◽  
Computational Models ◽  
Long Qt ◽  
Qt Syndrome

scholarly journals Do M-cells contribute significantly in T-wave morphology during normal and arrhythmogenesis conditions like short QT Syndrome?

2020 ◽  
Author(s):  
Ponnuraj Kirthi Priya ◽  
Srinivasan Jayaraman
Keyword(s):  
Cell Types ◽  
M Cells ◽  
Short Qt Syndrome ◽  
M Cell ◽  
T Wave ◽  
Wave Morphology ◽  
Qt Syndrome ◽  
Premature Beats ◽  
Low Amplitude ◽  
T Waves

AbstractAimsThis paper proposes to explain the mechanism of M-cells, particularly its role in the T-wave generation and its contribution to arrhythmogenesis in short QT syndrome 2 (SQTS2).MethodsA 2D transmural anisotropic ventricular model made up of three principal cell types were developed. Different setups in which: a) entire column of mid-myocardial (mid) cells, b) single island of cells c) two island of cells within the mid-layer d) single island of cells in endocardial (endo)-mid layer were considered as M-cells. These setups are stimulated to explain i) contribution of M-cells in T-wave morphology ii) arrhythmia generation phenomena under SQTS2 heterozygous gene mutation by creating pseudo ECGs from the tissue.ResultsFindings infer that setups with an entire layer of M-cells and a higher percentage of epicardial (epi) cells exhibit positive T-waves. Increasing the size of the island in M-cell island setups results in an increased positive T-peak. Placing the M-cell island in the bottom of the mid-layer produced low amplitude T-waves. Further, in two M-cell islands setup, a higher T-wave amplitude was observed when the islands are placed closer than far apart. Moving the M-cell island slightly into the endo layer increases the amplitude of the T-wave. Lastly, on including SQTS2 conditions and pacing with premature beats, an arrhythmia occurs only in those setups containing a layer of M-cells compared to M-cells island setup.ConclusionThese simulation findings paved the way for a better understanding of the M-cells functionality in T-wave morphology as well as promoting arrhythmogenesis under SQTS2 condition.

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 ◽  
...  
Keyword(s):  
Action Potential ◽  
Cardiac Myocytes ◽  
Action Potential Duration ◽  
Ionic Current ◽  
Induced Pluripotent Stem Cell ◽  
Cardiac Action Potential ◽  
Patient Specific ◽  
Cardiac Action ◽  
Qt Syndrome ◽  
Cardiac Action Potential Duration

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.

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