Intracellular Ca alternans: coordinated regulation by sarcoplasmic reticulum release, uptake, and leak

Biophysical Journal
Lai-Hua XieJames N Weiss


Beat-to-beat alternation in the cardiac intracellular Ca (Ca(i)) transient can drive action potential (AP) duration alternans, creating a highly arrhythmogenic substrate. Although a steep dependence of fractional sarcoplasmic reticulum (SR) Ca release on SR Ca load has been shown experimentally to promote Ca(i) alternans, theoretical studies predict that other factors are also important. Here we present an iterated map analysis of the coordinated effects of SR Ca release, uptake, and leak on the onset of Ca(i) alternans. Predictions were compared to numerical simulations using a physiologically realistic AP model as well as to AP clamp experiments in isolated patch-clamped rabbit ventricular myocytes exposed to 1), the Ca channel agonist BayK8644 (100 nM) to increase SR Ca load and release fraction, 2), overexpression of an adenoviral SERCA2a construct to increase SR Ca uptake, and 3), low-dose FK506 (20 microM) or ryanodine (1 microM) to increase SR Ca leak. Our findings show that SR Ca release, uptake, and leak all have independent direct effects that promote (release and leak) or suppress (uptake) Ca(i) alternans. However, since each factor affects the other by altering SR Ca load, the net balance of their direct and indirec...Continue Reading


Mar 1, 1991·Journal of Neuroscience Methods·J RaeM Watsky
Jan 27, 1994·The New England Journal of Medicine·David S RosenbaumR J Cohen
Nov 1, 1996·Cardiovascular Research·D E EulerB Olshansky
Aug 7, 1997·Journal of Theoretical Biology·N F Otani, R F Gilmour
Mar 17, 1999·Circulation·J M PastoreDavid S Rosenbaum
Dec 10, 1999·Biophysical Journal·E ChudinB Kogan
Mar 10, 2001·Journal of Cardiovascular Electrophysiology·M A WatanabeAlain Karma
May 10, 2001·Journal of Molecular and Cellular Cardiology·K DaviaS E Harding
Feb 21, 2002·Circulation·Eric J RashbaMichael R Gold
Mar 15, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Cristian DumitrescuRuth A Altschuld
Jan 23, 2003·Circulation·Peter TaggartJaswinder S Gill
Dec 4, 2003·Biophysical Journal·Yohannes ShiferawA Karma
Jan 31, 2004·Circulation Research·Mary E DíazDavid A Eisner
Mar 16, 2004·Circulation Research·Etienne J PruvotKenneth R Laurita
Feb 16, 2005·Annual Review of Physiology·Xander H T WehrensAndrew R Marks
Feb 16, 2005·Proceedings of the National Academy of Sciences of the United States of America·Didier X P BrochetHeping Cheng
Mar 24, 2005·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Yohannes ShiferawAlain Karma
May 5, 2006·Proceedings of the National Academy of Sciences of the United States of America·Stephan E LehnartAndrew R Marks
May 27, 2006·Circulation Research·James N WeissZhilin Qu
Mar 16, 2007·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Zhilin QuJames N Weiss


Dec 18, 2012·Pflügers Archiv : European journal of physiology·Elisa VenturiHiroshi Takeshima
May 6, 2009·Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences·Jussi T KoivumäkiMatti Weckström
Apr 3, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Vyacheslav M ShkrylL A Blatter
Jun 5, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Michael Nivala, Zhilin Qu
Apr 7, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Seth H WeinbergLeslie Tung
Dec 2, 2009·Circulation. Arrhythmia and Electrophysiology·Michael J CutlerDavid S Rosenbaum
Jan 8, 2011·Circulation Research·James N WeissZhilin Qu
Feb 27, 2014·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·Yuanfang XieDaisuke Sato
Oct 2, 2009·Chaos·Juan G Restrepo, Alain Karma
Apr 25, 2012·Annual Review of Biomedical Engineering·Trine Krogh-Madsen, David J Christini
Oct 1, 2014·Physics Reports·Zhilin QuJames N Weiss
May 12, 2010·Heart Rhythm : the Official Journal of the Heart Rhythm Society·David J Christini
Apr 13, 2010·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Jason D BayerNatalia A Trayanova
Aug 6, 2009·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Michael J Cutler, David S Rosenbaum
Jan 27, 2009·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Michael J Cutler, David S Rosenbaum
Sep 3, 2011·Cardiovascular Therapeutics·Lu PengJing-Tian Xie
Jul 22, 2014·Clinical and Experimental Pharmacology & Physiology·Joshua N Edwards, L A Blatter
Jul 22, 2010·Annals of Noninvasive Electrocardiology : the Official Journal of the International Society for Holter and Noninvasive Electrocardiology, Inc·Tuomo Nieminen, Richard L Verrier
Oct 22, 2013·British Journal of Pharmacology·Markus B SikkelAlexander R Lyon
Mar 25, 2014·Biophysical Journal·Yuanfang XieDaisuke Sato
Nov 8, 2011·Journal of Molecular and Cellular Cardiology·Ona Z LiuEric A Sobie
Mar 7, 2014·Journal of Zhejiang University. Science. B·Yunliang Zang, Ling Xia
Jul 14, 2011·Progress in Biophysics and Molecular Biology·Lucía RomeroJose M Ferrero
Jul 20, 2011·Journal of Molecular and Cellular Cardiology·Eric A Sobie, W J Lederer
Oct 30, 2012·Journal of Molecular and Cellular Cardiology·Zhilin QuJames N Weiss
Oct 24, 2014·Annual Review of Physiology·Zhilin Qu, James N Weiss
Dec 17, 2014·PLoS Computational Biology·Kelly C ChangNatalia A Trayanova
Oct 21, 2016·Scientific Reports·Zhilin QuMichael Nivala
Dec 11, 2014·Circulation. Arrhythmia and Electrophysiology·Bradley N PlummerKenneth R Laurita
Jun 18, 2010·Journal of Cardiovascular Pharmacology·Richard L Verrier, Tuomo Nieminen
Oct 28, 2019·International Journal of Molecular Sciences·Vera PaarLukas J Motloch
Mar 13, 2020·Frontiers in Pharmacology·Kornél KistamásDavid A Eisner
Aug 27, 2015·The Journal of Biological Chemistry·Mads T SøndergaardMichael T Overgaard
Jan 11, 2017·Computational and Mathematical Methods in Medicine·Jiaqi LiuXiaopeng Zhao
Dec 13, 2019·Computational and Mathematical Methods in Medicine·Jiaqi LiuLing Xia
Jul 23, 2020·Biophysics Reviews·Amanda L DennissNicole A Beard
Dec 31, 2020·Circulation Research·Jinhong WeiSr Wayne Chen
Jan 6, 2021·Pflügers Archiv : European journal of physiology·L A BlatterK Banach
Feb 17, 2021·Pflügers Archiv : European journal of physiology·Charia McKeeXun Ai

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