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Article ; Online: With a grain of salt: Sodium elevation and metabolic remodelling in heart failure.

Aksentijević, Dunja / Shattock, Michael J

Journal of molecular and cellular cardiology

2021 Volume 161, Page(s) 106–115

Abstract: Elevated intracellular Na ( ... ...

Abstract	Elevated intracellular Na (Na
MeSH term(s)	Animals ; Epoxy Compounds/pharmacology ; Heart Failure/drug therapy ; Heart Failure/metabolism ; Heart Failure/physiopathology ; Humans ; Myocardium/metabolism ; Sodium/metabolism
Chemical Substances	Epoxy Compounds ; Sodium (9NEZ333N27) ; etomoxir (MSB3DD2XP6)
Language	English
Publishing date	2021-08-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80157-4
ISSN	1095-8584 ; 0022-2828
ISSN (online)	1095-8584
ISSN	0022-2828
DOI	10.1016/j.yjmcc.2021.08.003
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Article ; Online: Empagliflozin improves cardiac energetics during ischaemia/reperfusion by directly increasing cardiac ketone utilization.

Chase, Dylan / Eykyn, Thomas R / Shattock, Michael J / Chung, Yu Jin

Cardiovascular research

2023 Volume 119, Issue 16, Page(s) 2672–2680

Abstract: Aims: Empagliflozin (EMPA), a potent inhibitor of the renal sodium-glucose cotransporter 2 and an effective treatment for Type 2 diabetes, has been shown to have cardioprotective effects, independent of improved glycaemic control. Several non-canonical ... ...

Abstract	Aims: Empagliflozin (EMPA), a potent inhibitor of the renal sodium-glucose cotransporter 2 and an effective treatment for Type 2 diabetes, has been shown to have cardioprotective effects, independent of improved glycaemic control. Several non-canonical mechanisms have been proposed to explain these cardiac effects, including increasing circulating ketone supply to the heart. This study aims to test whether EMPA directly alters cardiac ketone metabolism independent of supply. Methods and results: The direct effects of EMPA on cardiac function and metabolomics were investigated in Langendorff rat heart perfused with buffer containing 5 mM glucose, 4 mM β-hydroxybutyrate (βHb) and 0.4 mM intralipid, subject to low flow ischaemia/reperfusion. Cardiac energetics were monitored in situ using 31P NMR spectroscopy. Steady-state 13C labelling was performed by switching 12C substrates for 13C1 glucose or 13C4 βHb and 13C incorporation into metabolites determined using 2D 1H-13C HSQC NMR spectroscopy. EMPA treatment improved left ventricular-developed pressure during ischaemia and reperfusion compared to vehicle-treated hearts. In EMPA-treated hearts, total adenosine triphosphate (ATP) and phosphocreatine (PCr) levels, and Gibbs free energy for ATP hydrolysis were significantly higher during ischaemia and reperfusion. EMPA treatment did not alter the incorporation of 13C from glucose into glycolytic products lactate or alanine neither during ischaemia nor reperfusion. In ischaemia, EMPA led to a decrease in 13C1 glucose incorporation and a concurrent increase in 13C4 βHb incorporation into tricarboxylic acid (TCA) cycle intermediates succinate, citrate, and glutamate. During reperfusion, the concentration of metabolites originating from 13C1 glucose was similar to vehicle but those originating from 13C4 βHb remained elevated in EMPA-treated hearts. Conclusion: Our findings indicate that EMPA causes a switch in metabolism away from glucose oxidation towards increased ketone utilization in the rat heart, thereby improving function and energetics both during ischaemia and recovery during reperfusion. This preference of ketone utilization over glucose was observed under conditions of constant supply of substrate, suggesting that EMPA acts directly by modulating cardiac substrate preference, independent of substrate availability. The mechanisms underlying our findings are currently unknown, warranting further study.
MeSH term(s)	Rats ; Animals ; Diabetes Mellitus, Type 2 ; Glucose ; Adenosine Triphosphate/metabolism ; Ischemia ; Reperfusion
Chemical Substances	empagliflozin (HDC1R2M35U) ; Glucose (IY9XDZ35W2) ; Adenosine Triphosphate (8L70Q75FXE)
Language	English
Publishing date	2023-10-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80340-6
ISSN	1755-3245 ; 0008-6363
ISSN (online)	1755-3245
ISSN	0008-6363
DOI	10.1093/cvr/cvad157
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Article ; Online: Sensing Cytosolic DNA Lowers Blood Pressure by Direct cGAMP-Dependent PKGI Activation.

Su, Jie / Coleman, Pierre / Ntorla, Angeliki / Anderson, Rhys / Shattock, Michael J / Burgoyne, Joseph R

Circulation

2023 Volume 148, Issue 13, Page(s) 1023–1034

Abstract: Background: The major cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) has emerged as a key mediator of inflammation that underlies cardiovascular disease. On interaction with double-stranded DNA, cGAS generates the second messenger 2',3'-cyclic GMP- ... ...

Abstract	Background: The major cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) has emerged as a key mediator of inflammation that underlies cardiovascular disease. On interaction with double-stranded DNA, cGAS generates the second messenger 2',3'-cyclic GMP-AMP (cGAMP) that directly binds to and activates the stimulator of interferon genes, which in turn leads to enhanced expression of genes encoding interferons and proinflammatory cytokines. Here, we show that cGAMP generated by cGAS also directly activates PKGI (cGMP-dependent protein kinase 1), a mechanism that underlies crosstalk between inflammation and blood pressure regulation. Methods: The ability of cGAS and cGAMP to activate PKGI was assessed using molecular, cellular, and biochemical analyses, and in myography experiments, as well. The release of cGAMP from the endothelium was measured using an ELISA, and its uptake into the vascular smooth muscle was assessed using molecular and biochemical approaches, including the identification and targeting of specific cGAMP transporters. The blood pressure of wild-type and cGAS Results: The detection of cytosolic DNA by cGAS within the vascular endothelium leads to formation of cGAMP that was found to be actively extruded by MRP1 (multidrug resistance protein 1). Once exported, this cGAMP is then imported into neighboring vascular smooth muscle cells through the volume-regulated anion channel, where it can directly activate PKGI. The activation of PKGI by cGAMP mediates vasorelaxation that is dependent on the activity of MRP1 and volume-regulated anion channel, but independent of the canonical nitric oxide pathway. This mechanism of PKGI activation mediates lowering of blood pressure and contributes to hypotension and tissue hypoperfusion during sepsis. Conclusions: The activation of PKGI by cGAMP enables the coupling of blood pressure to cytosolic DNA sensing by cGAS, which plays a key role during sepsis by mediating hypotension and tissue hypoperfusion.
MeSH term(s)	Animals ; Mice ; Blood Pressure ; DNA/metabolism ; Nucleotidyltransferases/genetics ; Nucleotidyltransferases/metabolism ; Inflammation ; Hypotension
Chemical Substances	cyclic guanosine monophosphate-adenosine monophosphate ; DNA (9007-49-2) ; Nucleotidyltransferases (EC 2.7.7.-)
Language	English
Publishing date	2023-08-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80099-5
ISSN	1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
ISSN (online)	1524-4539
ISSN	0009-7322 ; 0069-4193 ; 0065-8499
DOI	10.1161/CIRCULATIONAHA.123.065547
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Article ; Online: Glutathione-dependent depalmitoylation of phospholemman by peroxiredoxin 6.

Howie, Jacqueline / Tulloch, Lindsay B / Brown, Elaine / Reilly, Louise / Ashford, Fiona B / Kennedy, Jennifer / Wypijewski, Krzysztof J / Aughton, Karen L / Mak, Jason K C / Shattock, Michael J / Fraser, Niall J / Fuller, William

Cell reports

2024 Volume 43, Issue 2, Page(s) 113679

Abstract: Phospholemman (PLM) regulates the cardiac sodium pump: PLM phosphorylation activates the pump whereas PLM palmitoylation inhibits its activity. Here, we show that the anti-oxidant protein peroxiredoxin 6 (Prdx6) interacts with and depalmitoylates PLM in ... ...

Abstract	Phospholemman (PLM) regulates the cardiac sodium pump: PLM phosphorylation activates the pump whereas PLM palmitoylation inhibits its activity. Here, we show that the anti-oxidant protein peroxiredoxin 6 (Prdx6) interacts with and depalmitoylates PLM in a glutathione-dependent manner. Glutathione loading cells acutely reduce PLM palmitoylation; glutathione depletion significantly increases PLM palmitoylation. Prdx6 silencing abolishes these effects, suggesting that PLM can be depalmitoylated by reduced Prdx6. In vitro, only recombinant Prdx6, among several peroxiredoxin isoforms tested, removes palmitic acid from recombinant palmitoylated PLM. The broad-spectrum depalmitoylase inhibitor palmostatin B prevents Prdx6-dependent PLM depalmitoylation in cells and in vitro. Our data suggest that Prdx6 is a thioesterase that can depalmitoylate proteins by nucleophilic attack via its reactive thiol, linking PLM palmitoylation and hence sodium pump activity to cellular glutathione status. We show that protein depalmitoylation can occur via a catalytic cysteine in which substrate specificity is determined by a protein-protein interaction.
MeSH term(s)	Peroxiredoxin VI ; Sodium-Potassium-Exchanging ATPase ; Membrane Proteins ; Glutathione ; Phosphoproteins
Chemical Substances	phospholemman (135541-82-1) ; Peroxiredoxin VI (EC 1.11.1.15) ; Sodium-Potassium-Exchanging ATPase (EC 7.2.2.13) ; Membrane Proteins ; Glutathione (GAN16C9B8O) ; Phosphoproteins
Language	English
Publishing date	2024-01-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2024.113679
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Article ; Online: Targeted degradation of zDHHC-PATs decreases substrate S-palmitoylation.

Bai, Mingjie / Gallen, Emily / Memarzadeh, Sarah / Howie, Jacqueline / Gao, Xing / Kuo, Chien-Wen S / Brown, Elaine / Swingler, Simon / Wilson, Sam J / Shattock, Michael J / France, David J / Fuller, William

PloS one

2024 Volume 19, Issue 3, Page(s) e0299665

Abstract: Reversible S-palmitoylation of protein cysteines, catalysed by a family of integral membrane zDHHC-motif containing palmitoyl acyl transferases (zDHHC-PATs), controls the localisation, activity, and interactions of numerous integral and peripheral ... ...

Abstract	Reversible S-palmitoylation of protein cysteines, catalysed by a family of integral membrane zDHHC-motif containing palmitoyl acyl transferases (zDHHC-PATs), controls the localisation, activity, and interactions of numerous integral and peripheral membrane proteins. There are compelling reasons to want to inhibit the activity of individual zDHHC-PATs in both the laboratory and the clinic, but the specificity of existing tools is poor. Given the extensive conservation of the zDHHC-PAT active site, development of isoform-specific competitive inhibitors is highly challenging. We therefore hypothesised that proteolysis-targeting chimaeras (PROTACs) may offer greater specificity to target this class of enzymes. In proof-of-principle experiments we engineered cell lines expressing tetracycline-inducible Halo-tagged zDHHC5 or zDHHC20, and evaluated the impact of Halo-PROTACs on zDHHC-PAT expression and substrate palmitoylation. In HEK-derived FT-293 cells, Halo-zDHHC5 degradation significantly decreased palmitoylation of its substrate phospholemman, and Halo-zDHHC20 degradation significantly diminished palmitoylation of its substrate IFITM3, but not of the SARS-CoV-2 spike protein. In contrast, in a second kidney derived cell line, Vero E6, Halo-zDHHC20 degradation did not alter palmitoylation of either IFITM3 or SARS-CoV-2 spike. We conclude from these experiments that PROTAC-mediated targeting of zDHHC-PATs to decrease substrate palmitoylation is feasible. However, given the well-established degeneracy in the zDHHC-PAT family, in some settings the activity of non-targeted zDHHC-PATs may substitute and preserve substrate palmitoylation.
MeSH term(s)	Humans ; Lipoylation ; Acyltransferases/genetics ; Acyltransferases/chemistry ; Spike Glycoprotein, Coronavirus/metabolism ; Cell Line ; Membrane Proteins/metabolism ; RNA-Binding Proteins/metabolism
Chemical Substances	spike protein, SARS-CoV-2 ; Acyltransferases (EC 2.3.-) ; Spike Glycoprotein, Coronavirus ; IFITM3 protein, human ; Membrane Proteins ; RNA-Binding Proteins
Language	English
Publishing date	2024-03-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0299665
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Article ; Online: Stimulated phosphorylation of ERK in mouse kidney mesangial cells is dependent upon expression of Cav3.1.

Pandi, Sudha Priya Soundara / Shattock, Michael J / Hendry, Bruce M / Sharpe, Claire C

BMC nephrology

2022 Volume 23, Issue 1, Page(s) 211

Abstract: Background: T-type calcium channels (TTCC) are low voltage activated channels that are widely expressed in the heart, smooth muscle and neurons. They are known to impact on cell cycle progression in cancer and smooth muscle cells and more recently, have ...

Abstract	Background: T-type calcium channels (TTCC) are low voltage activated channels that are widely expressed in the heart, smooth muscle and neurons. They are known to impact on cell cycle progression in cancer and smooth muscle cells and more recently, have been implicated in rat and human mesangial cell proliferation. The aim of this study was to investigate the roles of the different isoforms of TTCC in mouse mesangial cells to establish which may be the best therapeutic target for treating mesangioproliferative kidney diseases. METHODS: In this study, we generated single and double knockout (SKO and DKO) clones of the TTCC isoforms Ca Results: We demonstrate a complete loss of ERK1/2 phosphorylation in response to multiple stimuli (serum, PDGF, TGF-β1) in Ca Conclusion: This study confirms that TTCC are expressed in mouse mesangial cells and that they play a role in cell proliferation. Whereas the Ca
MeSH term(s)	Animals ; Calcium Channels, T-Type ; Humans ; Mesangial Cells/metabolism ; Mibefradil/metabolism ; Mibefradil/pharmacology ; Mice ; Phosphorylation ; Rats ; Transforming Growth Factor beta1/metabolism
Chemical Substances	Calcium Channels, T-Type ; Transforming Growth Factor beta1 ; Mibefradil (27B90X776A)
Language	English
Publishing date	2022-06-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2041348-8
ISSN	1471-2369 ; 1471-2369
ISSN (online)	1471-2369
ISSN	1471-2369
DOI	10.1186/s12882-022-02844-1
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Article ; Online: Autonomic conflict exacerbates long QT associated ventricular arrhythmias.

Winter, James / Tipton, Michael J / Shattock, Michael J

Journal of molecular and cellular cardiology

2018 Volume 116, Page(s) 145–154

Abstract: This study tested the hypothesis that concomitant sympathetic and parasympathetic stimulation ("autonomic conflict") may act as a trigger for arrhythmias in long QT syndrome (LQTS). Studies were performed in isolated innervated rabbit hearts treated with ...

Abstract	This study tested the hypothesis that concomitant sympathetic and parasympathetic stimulation ("autonomic conflict") may act as a trigger for arrhythmias in long QT syndrome (LQTS). Studies were performed in isolated innervated rabbit hearts treated with clofilium (100 nmol/L); a potassium channel blocker. The influence of vagus nerve stimulation (VNS) on spontaneous ventricular arrhythmias was assessed in the absence/presence of sustained noradrenaline perfusion (100 nmol/L) and with sudden adrenergic stress (injections of noradrenaline into the perfusion line). Hearts were instrumented for a pseudo-electrocardiogram and monophasic action potential recordings. VNS, which slows heart rate, was associated with a stimulation frequency-dependent incidence of spontaneous early after-depolarisations (EADs) and ventricular tachycardia (VT), best predicted by the duration of the electrocardiographic T-wave and by triangulation of the ventricular action potential. In the presence of sustained (steady-state) noradrenaline perfusion, the incidence of EADs and VT with VNS was decreased from 73/55% to 45/27%, respectively. However, sudden adrenergic stress, imposed during periods of sustained VNS, was associated with a transient increase in the incidence of severity of observed arrhythmias, as indicated by an increase in the average arrhythmias score (1.6 ± 0.4 vs. 2.1 ± 0.7, p = .01). Analysis of electrophysiological parameters suggests that sudden adrenergic stress is associated with a transient prolongation, and increased triangulation, of the ventricular action potential, which may predispose to triggered activity. This study demonstrates that autonomic conflict is a pro-arrhythmic stimulus in LQTS. However, combined adrenergic and parasympathetic stimulation has a complex relationship with arrhythmogenicity, with differences in the effects of steady-state adrenergic activation vs. sudden adrenergic stress.
MeSH term(s)	Action Potentials/drug effects ; Animals ; Arrhythmias, Cardiac/complications ; Arrhythmias, Cardiac/physiopathology ; Autonomic Nervous System/drug effects ; Autonomic Nervous System/physiopathology ; Heart Rate/drug effects ; Heart Ventricles/drug effects ; Heart Ventricles/physiopathology ; Long QT Syndrome/complications ; Long QT Syndrome/physiopathology ; Norepinephrine/pharmacology ; Rabbits ; Tachycardia, Ventricular/complications ; Tachycardia, Ventricular/physiopathology ; Vagus Nerve Stimulation
Chemical Substances	Norepinephrine (X4W3ENH1CV)
Language	English
Publishing date	2018-02-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80157-4
ISSN	1095-8584 ; 0022-2828
ISSN (online)	1095-8584
ISSN	0022-2828
DOI	10.1016/j.yjmcc.2018.02.001
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Article ; Online: Glutathione-dependent depalmitoylation of phospholemman by peroxiredoxin 6

Jacqueline Howie / Lindsay B. Tulloch / Elaine Brown / Louise Reilly / Fiona B. Ashford / Jennifer Kennedy / Krzysztof J. Wypijewski / Karen L. Aughton / Jason K.C. Mak / Michael J. Shattock / Niall J. Fraser / William Fuller

Cell Reports, Vol 43, Iss 2, Pp 113679- (2024)

2024

Abstract: Summary: Phospholemman (PLM) regulates the cardiac sodium pump: PLM phosphorylation activates the pump whereas PLM palmitoylation inhibits its activity. Here, we show that the anti-oxidant protein peroxiredoxin 6 (Prdx6) interacts with and ... ...

Abstract	Summary: Phospholemman (PLM) regulates the cardiac sodium pump: PLM phosphorylation activates the pump whereas PLM palmitoylation inhibits its activity. Here, we show that the anti-oxidant protein peroxiredoxin 6 (Prdx6) interacts with and depalmitoylates PLM in a glutathione-dependent manner. Glutathione loading cells acutely reduce PLM palmitoylation; glutathione depletion significantly increases PLM palmitoylation. Prdx6 silencing abolishes these effects, suggesting that PLM can be depalmitoylated by reduced Prdx6. In vitro, only recombinant Prdx6, among several peroxiredoxin isoforms tested, removes palmitic acid from recombinant palmitoylated PLM. The broad-spectrum depalmitoylase inhibitor palmostatin B prevents Prdx6-dependent PLM depalmitoylation in cells and in vitro. Our data suggest that Prdx6 is a thioesterase that can depalmitoylate proteins by nucleophilic attack via its reactive thiol, linking PLM palmitoylation and hence sodium pump activity to cellular glutathione status. We show that protein depalmitoylation can occur via a catalytic cysteine in which substrate specificity is determined by a protein-protein interaction.
Keywords	CP: Cell biology ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2024-02-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: Geometrical considerations in cardiac electrophysiology and arrhythmogenesis.

Winter, James / Shattock, Michael J

Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology

2015 Volume 18, Issue 3, Page(s) 320–331

Abstract: The rate of repolarization (RRepol) and so the duration of the cardiac action potential are determined by the balance of inward and outward currents across the cardiac membrane (net ionic current). Plotting action potential duration (APD) as a function ... ...

Abstract	The rate of repolarization (RRepol) and so the duration of the cardiac action potential are determined by the balance of inward and outward currents across the cardiac membrane (net ionic current). Plotting action potential duration (APD) as a function of the RRepol reveals an inverse non-linear relationship, arising from the geometric association between these two factors. From the RRepol-APD relationship, it can be observed that a longer action potential will exhibit a greater propensity to shorten, or prolong, for a given change in the RRepol (i.e. net ionic current), when compared with one that is initially shorter. This observation has recently been used to explain why so many interventions that prolong the action potential exert a greater effect at slow rates (reverse rate-dependence). In this article, we will discuss the broader implications of this simple principle and examine how common experimental observations on the electrical behaviour of the myocardium may be explained in terms of the RRepol-APD relationship. An argument is made, with supporting published evidence, that the non-linear relationship between the RRepol and APD is a fundamental, and largely overlooked, property of the myocardium. The RRepol-APD relationship appears to explain why interventions and disease with seemingly disparate mechanisms of action have similar electrophysiological consequences. Furthermore, the RRepol-APD relationship predicts that prolongation of the action potential, by slowing repolarization, will promote conditions of dynamic electrical instability, exacerbating several electrophysiological phenomena associated with arrhythmogenesis, namely, the rate dependence of dispersion of repolarization, APD restitution, and electrical alternans.
MeSH term(s)	Action Potentials/drug effects ; Animals ; Anti-Arrhythmia Agents/therapeutic use ; Arrhythmias, Cardiac/diagnosis ; Arrhythmias, Cardiac/drug therapy ; Arrhythmias, Cardiac/physiopathology ; Electrocardiography ; Electrophysiologic Techniques, Cardiac ; Heart Conduction System/drug effects ; Heart Conduction System/physiopathology ; Heart Rate/drug effects ; Humans ; Kinetics ; Models, Cardiovascular ; Nonlinear Dynamics
Chemical Substances	Anti-Arrhythmia Agents
Language	English
Publishing date	2015-11-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1449879-0
ISSN	1532-2092 ; 1099-5129
ISSN (online)	1532-2092
ISSN	1099-5129
DOI	10.1093/europace/euv307
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Article: Phospholemman: its role in normal cardiac physiology and potential as a druggable target in disease.

Shattock, Michael J

Current opinion in pharmacology

2009 Volume 9, Issue 2, Page(s) 160–166

Abstract: Phospholemman (PLM) is a member of the FXYD ('fix-it') family of proteins many of which have now been identified as tissue-specific regulators of the Na/K ATPase. PLM (FXYD1) is the primary sarcolemmal substrate for PKC and PKA in the heart. We have ... ...

Abstract	Phospholemman (PLM) is a member of the FXYD ('fix-it') family of proteins many of which have now been identified as tissue-specific regulators of the Na/K ATPase. PLM (FXYD1) is the primary sarcolemmal substrate for PKC and PKA in the heart. We have recently identified PLM as a novel accessory protein that forms part of the cardiac Na/K ATPase pump complex. PLM regulates Na/K pump activity in a way analogous to the regulation of SERCA by phospholamban-that is un-phosphorylated PLM exerts a tonic inhibition on the Na/K pump, while phosphorylated PLM relieves this inhibition and stimulates pump activity. This process is likely to be fundamentally important in the normal physiological regulation of the cell particularly at high heart rates and, as briefly reviewed in this article, is also likely to offer novel therapeutic targets for the treatment of diseases such as cardiac hypertrophy and heart failure.
MeSH term(s)	Animals ; Cardiomegaly/drug therapy ; Cardiomegaly/physiopathology ; Drug Delivery Systems ; Heart/physiology ; Heart Failure/drug therapy ; Heart Failure/physiopathology ; Humans ; Membrane Proteins/physiology ; Nitric Oxide/physiology ; Phosphoproteins/physiology ; Receptors, Adrenergic, beta/physiology ; Reperfusion Injury/physiopathology ; Sodium-Potassium-Exchanging ATPase/physiology
Chemical Substances	Membrane Proteins ; Phosphoproteins ; Receptors, Adrenergic, beta ; phospholemman (135541-82-1) ; Nitric Oxide (31C4KY9ESH) ; Sodium-Potassium-Exchanging ATPase (EC 7.2.2.13)
Language	English
Publishing date	2009-02-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2037057-X
ISSN	1471-4973 ; 1471-4892
ISSN (online)	1471-4973
ISSN	1471-4892
DOI	10.1016/j.coph.2008.12.015
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