The Subcellular Distribution of Ryanodine Receptors and L-Type Ca2+ Channels Modulates Ca2+ -Transient Properties and Spontaneous Ca2+ -Release Events in Atrial Cardiomyocytes

Frontiers in Physiology
Henry SutantoJordi Heijman

Abstract

Spontaneous Ca2+-release events (SCaEs) from the sarcoplasmic reticulum play crucial roles in the initiation of cardiac arrhythmias by promoting triggered activity. However, the subcellular determinants of these SCaEs remain incompletely understood. Structural differences between atrial and ventricular cardiomyocytes, e.g., regarding the density of T-tubular membrane invaginations, may influence cardiomyocyte Ca2+-handling and the distribution of cardiac ryanodine receptors (RyR2) has recently been shown to undergo remodeling in atrial fibrillation. These data suggest that the subcellular distribution of Ca2+-handling proteins influences proarrhythmic Ca2+-handling abnormalities. Here, we employ computational modeling to provide an in-depth analysis of the impact of variations in subcellular RyR2 and L-type Ca2+-channel distributions on Ca2+-transient properties and SCaEs in a human atrial cardiomyocyte model. We incorporate experimentally observed RyR2 expression patterns and various configurations of axial tubules in a previously published model of the human atrial cardiomyocyte. We identify an increased SCaE incidence for larger heterogeneity in RyR2 expression, in which SCaEs preferentially arise from regions of high local ...Continue Reading

References

Jul 1, 1969·The Journal of Cell Biology·N S McNutt, D W Fawcett
Feb 19, 2002·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Hanny MusaMark R Boyett
Jun 14, 2002·Cardiovascular Research·Bianca J J M BrundelHarry J G M Crijns
Oct 21, 2003·Nature Biotechnology·Marcus DybaStefan W Hell
May 1, 2004·American Journal of Physiology. Heart and Circulatory Physiology·C M LoughreyK E MacEachern
Apr 11, 2006·Biophysical Journal·Ye Chen-IzuLeighton T Izu
Apr 22, 2006·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Antonio VincentiStefano Pedretti
Feb 25, 2011·Journal of Molecular and Cellular Cardiology·Jordi HeijmanYoram Rudy
Sep 6, 2011·Journal of Molecular and Cellular Cardiology·Jabe M Best, Timothy J Kamp
Mar 1, 2012·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Tobias MüllerAnnette Kraegeloh
Apr 13, 2012·The Journal of Physiology·Johan HakeAndrew D McCulloch
Aug 31, 2012·Frontiers in Physiology·Alexandra Zahradníková, Ivan Zahradník
Nov 14, 2012·Journal of Molecular and Cellular Cardiology·Katharine M DibbAndrew W Trafford
Dec 19, 2013·Circulation·Sumeet S ChughChristopher J L Murray
Apr 26, 2014·Circulation Research·Peng-Sheng ChenStanley Nattel
Oct 21, 2014·The Journal of Clinical Investigation·Maura GreiserUlrich Schotten
Dec 18, 2014·Biophysical Journal·Mark A WalkerRaimond L Winslow
Jun 26, 2015·The Journal of Biological Chemistry·Florian HiessS R Wayne Chen
Oct 28, 2015·Circulation·Gregory A RothChristopher J L Murray
Jan 31, 2016·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Jordi HeijmanDobromir Dobrev
Feb 2, 2016·Journal of Molecular and Cellular Cardiology·Andrew P WescottGeorge S B Williams
Jun 14, 2016·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Andres EnriquezAdrian Baranchuk
Jul 13, 2016·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Andreas GoetteUNKNOWN Document Reviewers:
Sep 20, 2016·The Journal of Clinical Investigation·Sören BrandenburgStephan E Lehnart
Oct 25, 2016·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Rishi AroraJ Andrew Wasserstrom
May 23, 2017·Journal of Molecular and Cellular Cardiology·Xin YueJoshua I Goldhaber
Jun 9, 2017·Journal of Geriatric Cardiology : JGC·Carlos A MorilloXavier Jouven
Jun 10, 2017·Circulation Research·Andrew P LandstromXander H T Wehrens
Jun 23, 2018·Journal of the American Heart Association·Samuel GaliceDonald M Bers

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Citations

Aug 1, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Aurore LyonJoost Lumens
Apr 9, 2020·International Journal of Molecular Sciences·Bin LiuSándor Györke
Aug 9, 2020·Circulation Research·Jordi HeijmanDobromir Dobrev
Nov 10, 2020·Frontiers in Physiology·Márcia R VagosJoakim Sundnes
Dec 29, 2020·Frontiers in Physiology·Viviane Timmermann, Andrew D McCulloch
Oct 17, 2020·Annual Review of Physiology·Jordi HeijmanUlrich Schotten
Jul 25, 2021·International Journal of Molecular Sciences·Jieyun BaiJichao Zhao

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Methods Mentioned

BETA
confocal microscopy
scanning electron microscopy
super-resolution microscopy

Software Mentioned

GraphPad Prism
Huygens Professional

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