Heart failure leads to altered β2-adrenoceptor/cyclic adenosine monophosphate dynamics in the sarcolemmal phospholemman/Na,K ATPase microdomain.

Cardiovascular Research
Zeynep Bastug-ÖzelViacheslav Nikolaev

Abstract

Cyclic adenosine monophosphate (cAMP) regulates cardiac excitation-contraction coupling by acting in microdomains associated with sarcolemmal ion channels. However, local real time cAMP dynamics in such microdomains has not been visualized before. We sought to directly monitor cAMP in a microdomain formed around sodium-potassium ATPase (NKA) in healthy and failing cardiomyocytes and to better understand alterations of cAMP compartmentation in heart failure. A novel Förster resonance energy transfer (FRET)-based biosensor termed phospholemman (PLM)-Epac1 was developed by fusing a highly sensitive cAMP sensor Epac1-camps to the C-terminus of PLM. Live cell imaging in PLM-Epac1 and Epac1-camps expressing adult rat ventricular myocytes revealed extensive regulation of NKA/PLM microdomain-associated cAMP levels by β2-adrenoceptors (β2-ARs). Local cAMP pools stimulated by these receptors were tightly controlled by phosphodiesterase (PDE) type 3. In chronic heart failure following myocardial infarction, dramatic reduction of the microdomain-specific β2-AR/cAMP signals and β2-AR dependent PLM phosphorylation was accompanied by a pronounced loss of local PDE3 and an increase in PDE2 effects. NKA/PLM complex forms a distinct cAMP microdo...Continue Reading

References

Jun 19, 2001·Gene·R C BogaevA L Tucker
Aug 10, 2002·Proceedings of the National Academy of Sciences of the United States of America·Gilles CrambertKathi Geering
Oct 22, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Xue-Qian ZhangJoseph Y Cheung
Mar 8, 2003·Journal of Molecular and Cellular Cardiology·Fons VerdonckKarin R Sipido
Mar 27, 2003·American Journal of Physiology. Renal Physiology·Randall K Wetzel, Kathleen J Sweadner
Jul 3, 2004·The Journal of Biological Chemistry·Viacheslav O NikolaevMartin J Lohse
Dec 29, 2004·Cardiovascular Research·Benjamin d Z SilvermanMichael J Shattock
Apr 3, 2009·American Journal of Physiology. Cell Physiology·William FullerMichael J Shattock
Apr 4, 2009·Proceedings of the National Academy of Sciences of the United States of America·Alexander R LyonJulia Gorelik
Aug 20, 2010·Clinical and Translational Science·Joseph Y CheungJufang Wang
Mar 18, 2011·Nature Protocols·Sebastian BörnerViacheslav O Nikolaev
Aug 27, 2011·The Journal of Biological Chemistry·Lindsay B TullochWilliam Fuller
Aug 4, 2012·Circulation Research·Alessia PerinoEmilio Hirsch
Nov 28, 2012·Proceedings of the National Academy of Sciences of the United States of America·Mounir KhafagaDonald M Bers
Feb 7, 2013·Acta Physiologica·R K Perera, V O Nikolaev
Jul 3, 2013·Journal of the American College of Cardiology·Hind MehelAli El-Armouche
Aug 12, 2014·Cardiovascular Research·Andrii BoguslavskyiMichael J Shattock
Feb 3, 2015·Journal of Molecular and Cellular Cardiology·Naama H SleimanSteven E Cala
May 6, 2016·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Anders KalsenJens Bangsbo

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Citations

Sep 13, 2019·Journal of Cellular and Molecular Medicine·Yan-Rong ZhuDai-Min Zhang
Feb 28, 2020·Biochemical Society Transactions·Aleksandra JudinaPeter T Wright
Nov 15, 2019·Biochemical Society Transactions·Christina KlausenDagmar Wachten
Sep 20, 2020·Naunyn-Schmiedeberg's Archives of Pharmacology·Bernardo DolceCristina E Molina
Dec 19, 2019·Frontiers in Physiology·Vladimir DikolayevViacheslav O Nikolaev
Nov 14, 2020·Journal of Molecular and Cellular Cardiology·Aniella Abi-GergesGrégoire Vandecasteele
Feb 15, 2021·Journal of Molecular and Cellular Cardiology·Alexandra MadsenJustus Stenzig
Jul 28, 2021·Annual Review of Analytical Chemistry·David KlenermanAndrew Shevchuk

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