Protein kinase/phosphatase balance mediates the effects of increased late sodium current on ventricular calcium cycling

Basic Research in Cardiology
Jörg EiringhausThomas H Fischer

Abstract

Increased late sodium current (late INa) is an important arrhythmogenic trigger in cardiac disease. It prolongs cardiac action potential and leads to an increased SR Ca2+ leak. This study investigates the contribution of Ca2+/Calmodulin-dependent kinase II (CaMKII), protein kinase A (PKA) and conversely acting protein phosphatases 1 and 2A (PP1, PP2A) to this subcellular crosstalk. Augmentation of late INa (ATX-II) in murine cardiomyocytes led to an increase of diastolic Ca2+ spark frequency and amplitudes of Ca2+ transients but did not affect SR Ca2+ load. Interestingly, inhibition of both, CaMKII and PKA, attenuated the late INa-dependent induction of the SR Ca2+ leak. PKA inhibition additionally reduced the amplitudes of systolic Ca2+ transients. FRET-measurements revealed increased levels of cAMP upon late INa augmentation, which could be prevented by simultaneous inhibition of Na+/Ca2+-exchanger (NCX) suggesting that PKA is activated by Ca2+-dependent cAMP-production. Whereas inhibition of PP2A showed no effect on late INa-dependent alterations of Ca2+ cycling, additional inhibition of PP1 further increased the SR Ca2+ leak. In line with this, selective activation of PP1 yielded a strong reduction of the late INa-induced S...Continue Reading

References

Jan 1, 1989·Annual Review of Biochemistry·P Cohen
Dec 1, 1996·The Journal of Physiology·Y K JuP W Gage
May 1, 1997·The Journal of Physiology·C A Ward, W R Giles
Dec 4, 2003·Cardiovascular Drug Reviews·Md Shah AmranKeitaro Hashimoto
Sep 17, 2005·Progress in Biophysics and Molecular Biology·C A WardW R Giles
Mar 23, 2007·American Journal of Physiology. Cell Physiology·Eckard PichtDonald M Bers
Sep 15, 2007·Progress in Biophysics and Molecular Biology·Victor A Maltsev, Albertas Undrovinas
Aug 19, 2009·PLoS Biology·Davide CalebiroMartin J Lohse
May 22, 2010·Journal of the American College of Cardiology·Samuel SossallaLars S Maier
Oct 5, 2010·Current Protocols in Molecular Biology·Arthur EdelsteinNico Stuurman
Mar 18, 2011·Nature Protocols·Sebastian BörnerViacheslav O Nikolaev
Aug 30, 2012·Journal of Visualized Experiments : JoVE·Julia U SprengerViacheslav O Nikolaev
Sep 11, 2012·Angewandte Chemie·Jayanta ChatterjeeMaja Köhn
Jan 3, 2013·The Journal of Clinical Investigation·Andrew R Marks
Mar 19, 2013·Journal of Molecular and Cellular Cardiology·Lars S Maier, Samuel Sossalla
Apr 11, 2013·Journal of Molecular and Cellular Cardiology·Karl ToischerSamuel Sossalla
May 8, 2013·Current Opinion in Chemical Biology·Jayanta Chatterjee, Maja Köhn
Jun 12, 2013·Cardiovascular Research·John C ShryockLuiz Belardinelli
Oct 22, 2013·JAMA : the Journal of the American Medical Association·UNKNOWN World Medical Association
Apr 17, 2014·Handbook of Experimental Pharmacology·Charles AntzelevitchLuiz Belardinelli
Sep 1, 2014·Journal of Molecular and Cellular Cardiology·Can M SagBernhard Unsöld
Dec 3, 2014·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Luiz BelardinelliJohn C Shryock
May 21, 2015·Cardiovascular Research·Thomas H FischerSamuel Sossalla
Oct 5, 2016·ACS Chemical Biology·Sara FahsMaja Köhn
Jan 20, 2017·Basic Research in Cardiology·Carlotta RonchiAntonio Zaza
May 21, 2017·Basic Research in Cardiology·Olga EleftheriadouAndrew K Snabaitis
Jun 10, 2017·Circulation Research·Andrew P LandstromXander H T Wehrens
Jun 10, 2017·Basic Research in Cardiology·Stefanie Meyer-RoxlauAli El-Armouche
Sep 30, 2017·Journal of the American College of Cardiology·Shin WatanabeRoger J Hajjar
Jun 16, 2018·Basic Research in Cardiology·Jan BeckendorfJohannes Backs

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Citations

Feb 23, 2020·Basic Research in Cardiology·Steffen PabelSamuel Sossalla
Sep 29, 2020·Frontiers in Cell and Developmental Biology·Ting XinFang Hu
Sep 11, 2020·Basic Research in Cardiology·Alyssa GroganAikaterini Kontrogianni-Konstantopoulos
Oct 7, 2020·Journal of Receptor and Signal Transduction Research·Qiubei LuBinhao Wang
Apr 29, 2020·ACS Central Science·Maja Köhn
Dec 17, 2019·The Journal of Organic Chemistry·Malgorzata TrebaczMaja Köhn
Nov 4, 2021·Chinese Journal of Integrative Medicine·Jun-Yan XiaDong Li

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