Enhanced Sarcoplasmic Reticulum Ca2+ Leak and Increased Na+-Ca2+ Exchanger Function Underlie Delayed Afterdepolarizations in Patients With Chronic Atrial Fibrillation
Niels Voigt,Na Li,Qiongling Wang,Wei Wang,Andrew W. Trafford,Issam Abu-Taha,Qiang Sun,Thomas Wieland,Ursula Ravens,Stanley Nattel,Xander H.T. Wehrens,Dobromir Dobrev +11 more
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TL;DR: Enhanced SR Ca2+ leak through CaMKII-hyperphosphorylated RyR2, in combination with larger INCX for a given SR Ca 2+ release and increased diastolic [Ca2+]i-voltage coupling gain, causes AF-promoting atrial delayed afterdepolarizations/triggered activity in cAF patients.
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Abstract: Background—Delayed afterdepolarizations (DADs) carried by Na+-Ca2+-exchange current (INCX) in response to sarcoplasmic reticulum (SR) Ca2+ leak can promote atrial fibrillation (AF). The mechanisms leading to delayed afterdepolarizations in AF patients have not been defined. Methods and Results—Protein levels (Western blot), membrane currents and action potentials (patch clamp), and [Ca2+]i (Fluo-3) were measured in right atrial samples from 76 sinus rhythm (control) and 72 chronic AF (cAF) patients. Diastolic [Ca2+]i and SR Ca2+ content (integrated INCX during caffeine-induced Ca2+ transient) were unchanged, whereas diastolic SR Ca2+ leak, estimated by blocking ryanodine receptors (RyR2) with tetracaine, was ≈50% higher in cAF versus control. Single-channel recordings from atrial RyR2 reconstituted into lipid bilayers revealed enhanced open probability in cAF samples, providing a molecular basis for increased SR Ca2+ leak. Calmodulin expression (60%), Ca2+/calmodulin-dependent protein kinase-II (CaMKII) a...
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Citations
•Dissertation
Alternans and Atrial Fibrillation: From Cellular Mechanisms to Arrhythmogenesis
Kelly C Chang
- 30 Jun 2016
TL;DR: Simulations revealed that reduced ryanodine receptor (RyR2) inactivation, resulting in a steep sarcoplasmic reticulum (SR) Ca release-load relationship, was responsible for alternans at slower pacing rates, and the effect of these Ca-driven alternans (CDA) on arrhythmogenesis was explored using an anatomically realistic, 3D model of the human atria.
1
Mechanisms of spontaneous Ca<sup>2+</sup> release-mediated arrhythmia in a novel 3D human atrial myocyte model: II. Ca<sup>2+</sup>-handling protein variation
Elisa Grandi
- 17 Jul 2022
TL;DR: In this paper , a 3D human atrial myocyte model with spatially detailed Ca 2+ diffusion and transverse-axial tubule system (TATS) was applied to investigate the isolated and interactive effects of changes in expression and localization of key Ca 2 + -handling proteins and variable TATS density on Ca 2 - handling abnormality driven membrane instabilities.
1
Bioinformatics analysis of the circRNA-miRNA-mRNA network for atrial fibrillation
TL;DR: In this article , a circRNA-miRNA-hub gene subnetwork with 10 regulatory axes was constructed to describe the interactions among the differential circRNAs, miRNA, and hub genes.
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The European Network for Translational Research in Atrial Fibrillation
Stéphane N. Hatem,Ulrich Schotten,Stephan Rohr,Dobromir Dobrev,Ursula Ravens,A. Goette,Burkert Pieske,Jens Kockskämper,U. Lendeckel,Barbara Casadei,Paulus Kirchhof,Frank-Ulrich Müller,Pierre Jais,A. Oto,A. John Camm +14 more
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TL;DR: Progress in the diagnosis, prevention and treatment of AF requires highly integrative research from the benchtop to bedside and from specific signaling pathways and electrophysiological mechanisms to population-based studies.
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Effect of angiotensin receptor-neprilysin inhibitor on atrial electrical instability in atrial fibrillation
Tianyu Zhu,Wen-Chao Zhang,Quan Yang,Ning Wang,Yuwei Fu,Yan Li,Guanliang Cheng,Liang Wang,Xian Zhang,Hongying Yao,Xing-Lan Sun,Yu Lu Chen,Xiaohui Wu,Xue-Jiao Chen,Xiaohui Liu +14 more
TL;DR: In this paper , the effect of angiotensin receptor-neprilysin inhibitor (ARNI) on atrial electrical instability and structural remodeling in patients with atrial fibrillation was investigated.
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