Abstract
The Na(+)/Ca(2+) exchanger (NCX) has been implied to cause arrhythmias. To date, information on the role of NCX in arrhythmogenesis derived from models with increased NCX expression, hypertrophy, and heart failure. Furthermore, the exact mechanism by which NCX exerts its potentially proarrhythmic effect, ie, by promoting early afterdepolarization (EAD) or delayed afterdepolarization (DAD) or both, is unknown. We investigated isolated cardiomyocytes from a murine model with heterozygous knockout of NCX (hetKO) using the patch clamp and Ca(2+) imaging techniques. Action potential duration was shorter in hetKO with IKtot not being increased. The rate of spontaneous Ca(2+) release events and the rate of DADs were unaltered; however, DADs had lower amplitude in hetKO. A DAD triggered a spontaneous action potential significantly less often in hetKO when compared with wild-type. The occurrence of EADs was also drastically reduced in hetKO. ICa activity was reduced in hetKO, an effect that was abolished in the presence of the Ca(2+) buffer BAPTA. Genetic suppression of NCX reduces both EADs and DADs. The following molecular mechanisms apply: (1) Although the absolute number of DADs is unaffected, an impaired translation of DADs into sp...Continue Reading
References
Nov 1, 1986·The Journal of Clinical Investigation·E MarbanW G Wier
May 1, 1997·Cardiovascular Research·P G VoldersB Szabo
Jun 1, 1997·The Journal of General Physiology·S Adachi-AkahaneM Morad
Nov 9, 2000·The Journal of Biological Chemistry·U KirchheferL R Jones
Jul 17, 2001·American Journal of Physiology. Heart and Circulatory Physiology·J MészárosG Hart
Sep 5, 2001·Nature Medicine·D NuyensP Carmeliet
Mar 6, 2002·British Journal of Pharmacology·Hikaru TanakaKoki Shigenobu
Jul 27, 2002·Circulation Research·Hannes ReuterKenneth D Philipson
Dec 14, 2002·Basic Research in Cardiology·Donald M BersKlaus Schlotthauer
Dec 3, 2003·The Journal of Physiology·Hannes ReuterJoshua I Goldhaber
Jan 23, 2004·Cardiovascular Research·Michiel J Janse
Mar 20, 2004·Trends in Cardiovascular Medicine·Steven M Pogwizd, Donald M Bers
Apr 28, 2004·The Journal of General Physiology·Dmytro IsaevRoman Shirokov
Aug 17, 2004·Circulation Research·Scott A HendersonKenneth D Philipson
Oct 27, 2004·British Journal of Pharmacology·Zsolt A NagyAndrás Varró
Aug 9, 2005·Naunyn-Schmiedeberg's Archives of Pharmacology·Péter BirinyiPéter P Nánási
Nov 19, 2005·Circulation Research·Christian PottJoshua I Goldhaber
Mar 21, 2006·Cardiovascular Research·Peter M R OrthDavid Fedida
Nov 23, 2006·Biophysical Journal·Christian PottKenneth D Philipson
Apr 21, 2007·Annals of the New York Academy of Sciences·Christian PottKenneth D Philipson
Apr 21, 2007·Annals of the New York Academy of Sciences·Karin R SipidoMarc A Vos
Mar 17, 2009·Basic Research in Cardiology·Christoph WaldeyerPaulus Kirchhof
Jun 11, 2009·Molecular Pharmacology·Genaro BarrientosIsaac N Pessah
Aug 28, 2010·Journal of Cardiac Failure·Maria C JordanKenneth P Roos
Nov 15, 2011·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Peter MilbergLars Eckardt
Feb 14, 2012·Basic Research in Cardiology·Christian PottFrank U Müller
Apr 27, 2013·Cardiovascular Research·Zhilin QuJames N Weiss
Oct 3, 2013·Current Medicinal Chemistry·N BogeholzC Pott
Citations
Jan 29, 2016·Basic Research in Cardiology·J S SchulteF U Müller
Oct 11, 2016·PloS One·Sophie Le PageFabrice Prunier
Oct 28, 2016·Circulation Journal : Official Journal of the Japanese Circulation Society·Mari IchikawaMinoru Horie
Feb 12, 2017·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Eric DuongStanley Nattel
May 13, 2017·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Sven KaeseLars Eckardt
Sep 28, 2017·Channels·Juejin WangTuck Wah Soong
May 9, 2018·Journal of Cardiovascular Pharmacology·Po-Cheng ChangChung-Chuan Chou
Aug 10, 2018·Fundamental & Clinical Pharmacology·Nils BögeholzLars Eckardt
Nov 20, 2016·EMBO Molecular Medicine·Harsha D DevallaRobert Passier
Jun 24, 2017·PloS One·Sven KaeseLars Eckardt
Nov 20, 2018·Frontiers in Physiology·Jian-Cheng ZhangPeng-Li Zhu
Oct 7, 2017·Frontiers in Pharmacology·Nils BögeholzFrank U Müller
Sep 7, 2018·Frontiers in Pharmacology·Nils BögeholzJan S Schulte
Oct 4, 2016·American Journal of Physiology. Heart and Circulatory Physiology·F HohendannerL A Blatter
Jan 24, 2020·Proceedings of the National Academy of Sciences of the United States of America·Ewan D FowlerMark B Cannell
Nov 15, 2018·Frontiers in Physiology·Shanna Hamilton, Dmitry Terentyev
Jul 7, 2020·Circulation. Arrhythmia and Electrophysiology·Jungmin HwangBum-Rak Choi
Feb 20, 2020·Cell Calcium·Kyle ScrantonMichela Ottolia
Jan 15, 2020·Cell Calcium·Caglar Gök, William Fuller
Dec 9, 2017·Journal of Molecular and Cellular Cardiology·Lili WangBjorn C Knollmann
Jun 3, 2021·PLoS Neglected Tropical Diseases·Artur Santos-MirandaDanilo Roman-Campos
Sep 3, 2021·Journal of the American Heart Association·Sabine LotteauJoshua I Goldhaber