Activation of reverse Na+-Ca2+ exchange by the Na+ current augments the cardiac Ca2+ transient: evidence from NCX knockout mice.

The Journal of Physiology
Robert LarbigKenneth D Philipson

Abstract

The hypothesis that Na(+) influx during the action potential (AP) activates reverse Na(+)-Ca(2+) exchange (NCX) and subsequent entry of trigger Ca(2+) is controversial. We tested this hypothesis by monitoring intracellular Ca(2+) before and after selective inactivation of I(Na) prior to a simulated action potential in patch-clamped ventricular myocytes isolated from adult wild-type (WT) and NCX knockout (KO) mice. First, we inactivated I(Na) using a ramp prepulse to 45 mV. In WT cells, inactivation of I(Na) decreased the Ca(2+) transient amplitude by 51.1 +/- 4.6% (P < 0.001, n = 14) and reduced its maximum release flux by 53.0 +/- 4.6% (P < 0.001, n = 14). There was no effect on diastolic Ca(2+). In striking contrast, Ca(2+) transients in NCX KO cardiomyocytes were unaffected by the presence or absence of I(Na) (n = 8). We obtained similar results when measuring trigger Ca(2+) influx in myocytes with depleted sarcoplasmic reticulum. In WT cells, inactivation of I(Na) decreased trigger Ca(2+) influx by 37.8 +/- 6% and maximum rate of flux by 30.6 +/- 7.7% at 2.5 mm external Ca(2+) (P < 0.001 and P < 0.05, n = 9). This effect was again absent in the KO cells (n = 8). Second, exposure to 10 mum tetrodotoxin to block I(Na) also re...Continue Reading

References

Apr 20, 1990·Science·W J LedererR W Hadley
Nov 1, 1985·The American Journal of Physiology·R Mitra, M Morad
Feb 1, 1994·The Journal of Physiology·P Lipp, E Niggli
Aug 1, 1996·The American Journal of Physiology·A M Vites, J A Wasserstrom
Jun 1, 1997·The Journal of General Physiology·S Adachi-AkahaneM Morad
Jul 3, 1999·Physiological Reviews·M P Blaustein, W J Lederer
Jun 9, 2000·Annual Review of Physiology·K D Philipson, D A Nicoll
Jan 24, 2002·Nature·Donald M Bers
Aug 17, 2004·Circulation Research·Scott A HendersonKenneth D Philipson
May 9, 2006·Biophysical Journal·Glenn T LinesOle M Sejersted
Feb 17, 2009·The Journal of Physiology·Gordon B Drummond

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Citations

Jul 23, 2011·Basic Research in Cardiology·Chin-Feng TsaiYi-Jen Chen
Jun 19, 2012·Wiener medizinische Wochenschrift·Nils BögeholzChristian Pott
Jun 24, 2011·Cardiovascular Research·Przemysław B Radwański, Steven Poelzing
Jan 22, 2013·Cardiovascular Research·Markus B SikkelKenneth T MacLeod
Feb 13, 2013·Cardiovascular Research·David R L ScrivenEdwin D W Moore
Jan 2, 2014·Journal of Molecular and Cellular Cardiology·Jaime DeSantiagoKathrin Banach
Mar 29, 2014·Critical Care : the Official Journal of the Critical Care Forum·Andrew KoestersMark M Rich
Nov 8, 2011·Protoplasma·Parisa AsghariEdwin D W Moore
Jun 14, 2012·Journal of Pharmacological and Toxicological Methods·Sonia GoineauGuillaume Froget
Dec 30, 2014·Cardiovascular Research·Przemysław B RadwańskiSándor Györke
Feb 15, 2017·The Journal of Physiology·Rengasayee VeeraraghavanPrzemysław B Radwański
Jun 15, 2018·The Journal of General Physiology·DeAnalisa C JonesEric A Sobie
Dec 6, 2018·Pacing and Clinical Electrophysiology : PACE·Maneesh K RaiKatta M Girisha
Apr 13, 2012·The Journal of Physiology·Johan HakeAndrew D McCulloch
May 26, 2018·The Journal of General Physiology·Megan KoleskePrzemysław B Radwański
Apr 28, 2017·Current Heart Failure Reports·Ornella ManfraWilliam E Louch
Feb 6, 2016·PloS One·Lukas Jaroslaw MotlochUta C Hoppe
Oct 26, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Cynthia GershomeGlen F Tibbits
Nov 13, 2015·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Raimond L WinslowJoseph L Greenstein
Mar 17, 2015·The Journal of Physiology·Michael J ShattockZi-Jian Xie
May 3, 2016·European Journal of Heart Failure·Uwe PrimessnigFrank R Heinzel
Jun 26, 2020·Frontiers in Pharmacology·Junli ZhaoWenkuan Xin
Dec 2, 2020·Channels·Kornél KistamásPéter P Nánási
Dec 5, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Martin LaasmaaMarko Vendelin
Jan 15, 2020·Cell Calcium·Caglar Gök, William Fuller
Jun 28, 2021·Journal of Molecular and Cellular Cardiology·Nimra GilaniKaie Ojamaa

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