Regulation of Ca2+ and electrical alternans in cardiac myocytes: role of CAMKII and repolarizing currents

American Journal of Physiology. Heart and Circulatory Physiology
Leonid Livshitz, Yoram Rudy

Abstract

Alternans of cardiac repolarization is associated with arrhythmias and sudden death. At the cellular level, alternans involves beat-to-beat oscillation of the action potential (AP) and possibly Ca(2+) transient (CaT). Because of experimental difficulty in independently controlling the Ca(2+) and electrical subsystems, mathematical modeling provides additional insights into mechanisms and causality. Pacing protocols were conducted in a canine ventricular myocyte model with the following results: 1) CaT alternans results from refractoriness of the sarcoplasmic reticulum Ca(2+) release system; alternation of the L-type calcium current has a negligible effect; 2) CaT-AP coupling during late AP occurs through the sodium-calcium exchanger and underlies AP duration (APD) alternans; 3) increased Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activity extends the range of CaT and APD alternans to slower frequencies and increases alternans magnitude; its decrease suppresses CaT and APD alternans, exerting an antiarrhythmic effect; and 4) increase of the rapid delayed rectifier current (I(Kr)) also suppresses APD alternans but without suppressing CaT alternans. Thus CaMKII inhibition eliminates APD alternans by eliminating its cau...Continue Reading

References

Jan 1, 1991·Circulation Research·C H OrchardM R Boyett
Dec 21, 1985·Journal of Theoretical Biology·D AdlerY Mahler
Nov 1, 1988·The Journal of Physiology·D J Beuckelmann, W G Wier
Sep 1, 1987·The American Journal of Physiology·D Adler, Y Mahler
Jan 27, 1994·The New England Journal of Medicine·David S RosenbaumR J Cohen
Jan 31, 1998·Science·P De Koninck, H Schulman
Nov 14, 1998·The American Journal of Physiology·Marcus L KollerRobert F Gilmour
Mar 17, 1999·Circulation·J M PastoreDavid S Rosenbaum
Nov 24, 1999·Nature Cell Biology·F DelPrincipeErnst Niggli
Dec 10, 1999·Biophysical Journal·E ChudinB Kogan
Sep 20, 2000·American Journal of Physiology. Heart and Circulatory Physiology·Lars S MaierB Pieske
Jan 11, 2000·Circulation Research·D A EisnerA W Trafford
Dec 14, 2001·Biochemical and Biophysical Research Communications·K U Bayer, H Schulman
Jan 15, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Jeffrey J FoxRobert F Gilmour
Apr 5, 2002·The Biochemical Journal·Andy Hudmon, H Schulman
Sep 18, 2002·Journal of Molecular and Cellular Cardiology·Jaime DeSantiagoDonald M Bers
Sep 25, 2002·Physiological Reviews·Michael Fill, Julio A Copello
Dec 4, 2003·Biophysical Journal·Yohannes ShiferawA Karma
Feb 14, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Fei HuaRobert F Gilmour
Feb 14, 2004·Circulation Research·Fei Hua, Robert F Gilmour
Mar 16, 2004·Circulation Research·Xander H T WehrensAndrew R Marks
Mar 16, 2004·Circulation Research·Etienne J PruvotKenneth R Laurita
Jun 5, 2004·Trends in Cardiovascular Medicine·Mark E Anderson
Dec 2, 2004·Experimental Physiology·D A EisnerA W Trafford
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
Mar 29, 2005·Nature Medicine·Rong ZhangMark E Anderson
Apr 12, 2005·Molecular Interventions·Harm J KnotOle H Petersen
Jun 14, 2005·Progress in Biophysics and Molecular Biology·J Sneyd, M Falcke
Jul 20, 2005·Journal of Molecular and Cellular Cardiology·Xiaoping WanDavid S Rosenbaum
Jul 30, 2005·Circulation Research·Long-Sheng SongStephen F Vatner
Sep 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·Zuzana KubalovaSandor Gyorke
Jan 18, 2006·Journal of the American College of Cardiology·Sanjiv M Narayan
Mar 28, 2006·American Journal of Physiology. Heart and Circulatory Physiology·K H W J ten Tusscher, A V Panfilov
May 27, 2006·Circulation Research·James N WeissZhilin Qu
Aug 12, 2006·Circulation Research·Daisuke SatoAlain Karma
Nov 30, 2006·Annals of the New York Academy of Sciences·Lance D WilsonDavid S Rosenbaum

Citations

Apr 22, 2009·Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences·David P Nickerson, Martin L Buist
May 6, 2009·Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences·Jussi T KoivumäkiMatti Weckström
Apr 7, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Seth H WeinbergLeslie Tung
Jun 15, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Martin FinkDenis Noble
Aug 14, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Byron N RobertsColleen E Clancy
Jan 27, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Keith F DeckerYoram Rudy
Jul 12, 2011·Physiological Reviews·Jeffrey R EricksonMark E Anderson
Jun 9, 2012·Circulation Research·Paari Dominic SwaminathanMark E Anderson
Sep 27, 2013·PLoS Computational Biology·John C WilliamsEmilia Entcheva
Dec 27, 2011·Critical Reviews in Biomedical Engineering·Robert K Amanfu, Jeffrey J Saucerman
Jun 17, 2011·Mathematical Biosciences and Engineering : MBE·Aslak TveitoAndrew D McCulloch
Aug 26, 2014·Computers in Biology and Medicine·Benjamin Bhattacharya-GhoshVanessa Díaz-Zuccarini
Jul 30, 2014·Life Sciences·Patric GlynnThomas J Hund
Nov 13, 2015·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Raimond L WinslowJoseph L Greenstein
Apr 5, 2012·The Journal of Physiology·Denis NoblePenelope J Noble
Jun 23, 2012·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Xiaoping WanDavid S Rosenbaum
Jan 2, 2016·Progress in Biophysics and Molecular Biology·Michael ClerxPaul G A Volders
Feb 25, 2011·Journal of Molecular and Cellular Cardiology·Jordi HeijmanYoram Rudy
Mar 23, 2010·Progress in Biophysics and Molecular Biology·Martin FinkNicolas P Smith
Mar 30, 2010·Mathematical Biosciences·George S B WilliamsM Saleet Jafri
Jul 5, 2008·Heart Failure Clinics·Roy C P KerckhoffsAndrew D McCulloch
Mar 13, 2016·Journal of Theoretical Biology·Ning WeiElena G Tolkacheva
May 18, 2010·Basic & Clinical Pharmacology & Toxicology·Martin Fink, Denis Noble
Mar 7, 2014·Journal of Zhejiang University. Science. B·Yun-Liang Zang, Ling Xia
Jun 28, 2011·Progress in Biophysics and Molecular Biology·Jonathan CooperSteven A Niederer
Apr 9, 2009·Progress in Biophysics and Molecular Biology·Sandeep S HothiChristopher L-H Huang
Mar 4, 2009·Biophysical Journal·Yasmin L HashambhoyJoseph L Greenstein
Apr 29, 2014·Frontiers in Pharmacology·Joseph L GreensteinRaimond L Winslow
Jan 23, 2015·Frontiers in Physiology·Jonathan CooperGary R Mirams
Dec 17, 2014·PLoS Computational Biology·Kelly C ChangNatalia A Trayanova
Aug 26, 2016·Biophysical Journal·Tashalee R BrownDavid J Christini
Oct 11, 2017·Physiological Reports·Andreas MayerStefan Luther
May 28, 2017·American Journal of Physiology. Heart and Circulatory Physiology·Jakub TomekJordi Heijman
Dec 11, 2014·Circulation. Arrhythmia and Electrophysiology·Bradley N PlummerKenneth R Laurita
Feb 19, 2017·Circulation. Arrhythmia and Electrophysiology·Amara Greer-ShortSeth H Weinberg
Oct 5, 2010·Critical Care Medicine·Quan-Yu ZhangJian-Ming Pei
Apr 1, 2009·Journal of Cardiovascular Pharmacology·Donald M Bers, Eleonora Grandi
Apr 29, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Donglin GuoGan-Xin Yan
May 27, 2014·American Journal of Physiology. Heart and Circulatory Physiology·Hirofumi MitsuyamaHiroyuki Tsutsui
Jul 2, 2017·Medicina·Giedrius Kanaporis, Lothar A Blatter
Sep 21, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ming-Yang WangFan-Hao Meng
Apr 24, 2017·JACC. Basic to Translational Science·Lance D Wilson, Kenneth R Laurita

Related Concepts

Nerve Impulses
Metazoa
Cardiac Arrhythmia
Calcium
In Silico
Canis familiaris
Cavia porcellus
Cardiac Conduction System
Potassium
Research Methodology

Related Feeds

Antiarrhythmic Agents: Mechanisms of Action

Understanding the mechanism of action of antiarrhythmic agents is essential in developing new medications as treatment of cardiac arrhythmias is currently limited by the reduced availability of safe and effective drugs. Discover the latest research on Antiarrhythmic Agents: Mechanism of Action here.

Anti-Arrhythmic Drug Therapies

Anti-arrhythmic drugs are used to prevent abnormal heart rhythms. These medications are used in conditions including, ventricular tachycardia, ventricular fibrillation and atrial fibrillation. Discover the latest research on anti-arrhythmic drug therapies here.

Arrhythmia

Arrhythmias are abnormalities in heart rhythms, which can be either too fast or too slow. They can result from abnormalities of the initiation of an impulse or impulse conduction or a combination of both. Here is the latest research on arrhythmias.

Cardiac Conduction System

The cardiac conduction system is a specialized tract of myocardial cells responsible for maintaining normal cardiac rhythm. Discover the latest research on the cardiac conduction system here.

Atrial Fibrillation

Atrial fibrillation is a common arrhythmia that is associated with substantial morbidity and mortality, particularly due to stroke and thromboembolism. Here is the latest research.