title: Kcnj11Ablation Is Associated With Increased Nitro-Oxidative Stress During Ischemia-Reperfusion Injury: Implications for Human Ischemic Cardiomyopathy.
abstract: BACKGROUND
  Despite increased secondary cardiovascular events in patients with ischemic cardiomyopathy (ICM), the expression of innate cardiac protective molecules in the hearts of patients with ICM is incompletely characterized. Therefore, we used a nonbiased RNAseq approach to determine whether differences in cardiac protective molecules occur with ICM.
  
  
  RESULTS
  RNAseq analysis of human control and ICM left ventricular samples demonstrated a significant decrease inKCNJ11expression with ICM.KCNJ11encodes the Kir6.2 subunit of the cardioprotective KATPchannel. Using wild-type mice andkcnj11-deficient (kcnj11-null) mice, we examined the effect ofkcnj11expression on cardiac function during ischemia-reperfusion injury. Reactive oxygen species generation increased inkcnj11-null hearts above that found in wild-type mice hearts after ischemia-reperfusion injury. Continuous left ventricular pressure measurement during ischemia and reperfusion demonstrated a more compromised diastolic function inkcnj11-null compared with wild-type mice during reperfusion. Analysis of key calcium-regulating proteins revealed significant differences inkcnj11-null mice. Despite impaired relaxation,kcnj11-null hearts increased phospholamban Ser16 phosphorylation, a modification that results in the dissociation of phospholamban from sarcoendoplasmic reticulum Ca2+, thereby increasing sarcoendoplasmic reticulum Ca2+-mediated calcium reuptake. However,kcnj11-null mice also had increased 3-nitrotyrosine modification of the sarcoendoplasmic reticulum Ca2+-ATPase, a modification that irreversibly impairs sarcoendoplasmic reticulum Ca2+function, thereby contributing to diastolic dysfunction.
  
  
  CONCLUSIONS
  KCNJ11expression is decreased in human ICM. Lack ofkcnj11expression increases peroxynitrite-mediated modification of the key calcium-handling protein sarcoendoplasmic reticulum Ca2+-ATPase after myocardial ischemia-reperfusion injury, contributing to impaired diastolic function. These data suggest a mechanism for ischemia-induced diastolic dysfunction in patients with ICM.
authors.affiliation: From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine (D.M.R., C.M.S.), Division of Cardiac Surgery, Department of Surgery (T.A.), Division of Cardiovascular Medicine (T. N., E. C., Y.R.S., D.R., C.L.G., Q.S.W, R.J.G.), Department of Pharmacology and Department of Pathology, Immunology, and Microbiology (R.J.G.), Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine (D.M.R., C.M.S.), Division of Cardiac Surgery, Department of Surgery (T.A.), Division of Cardiovascular Medicine (T. N., E. C., Y.R.S., D.R., C.L.G., Q.S.W, R.J.G.), Department of Pharmacology and Department of Pathology, Immunology, and Microbiology (R.J.G.), Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Novitskaya
authors.affiliation: From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine (D.M.R., C.M.S.), Division of Cardiac Surgery, Department of Surgery (T.A.), Division of Cardiovascular Medicine (T. N., E. C., Y.R.S., D.R., C.L.G., Q.S.W, R.J.G.), Department of Pharmacology and Department of Pathology, Immunology, and Microbiology (R.J.G.), Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Debra G
authors.initials: DG
authors.lastname: Wheeler
authors.affiliation: From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine (D.M.R., C.M.S.), Division of Cardiac Surgery, Department of Surgery (T.A.), Division of Cardiovascular Medicine (T. N., E. C., Y.R.S., D.R., C.L.G., Q.S.W, R.J.G.), Department of Pharmacology and Department of Pathology, Immunology, and Microbiology (R.J.G.), Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Zhaobin
authors.initials: Z
authors.lastname: Xu
authors.affiliation: From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine (D.M.R., C.M.S.), Division of Cardiac Surgery, Department of Surgery (T.A.), Division of Cardiovascular Medicine (T. N., E. C., Y.R.S., D.R., C.L.G., Q.S.W, R.J.G.), Department of Pharmacology and Department of Pathology, Immunology, and Microbiology (R.J.G.), Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Elena
authors.initials: E
authors.lastname: Chepurko
authors.affiliation: From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine (D.M.R., C.M.S.), Division of Cardiac Surgery, Department of Surgery (T.A.), Division of Cardiovascular Medicine (T. N., E. C., Y.R.S., D.R., C.L.G., Q.S.W, R.J.G.), Department of Pharmacology and Department of Pathology, Immunology, and Microbiology (R.J.G.), Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Ryan
authors.initials: R
authors.lastname: Huttinger
authors.affiliation: From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine (D.M.R., C.M.S.), Division of Cardiac Surgery, Department of Surgery (T.A.), Division of Cardiovascular Medicine (T. N., E. C., Y.R.S., D.R., C.L.G., Q.S.W, R.J.G.), Department of Pharmacology and Department of Pathology, Immunology, and Microbiology (R.J.G.), Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Heng
authors.initials: H
authors.lastname: He
authors.affiliation: From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine (D.M.R., C.M.S.), Division of Cardiac Surgery, Department of Surgery (T.A.), Division of Cardiovascular Medicine (T. N., E. C., Y.R.S., D.R., C.L.G., Q.S.W, R.J.G.), Department of Pharmacology and Department of Pathology, Immunology, and Microbiology (R.J.G.), Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Saradhadevi
authors.initials: S
authors.lastname: Varadharaj
authors.affiliation: From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine (D.M.R., C.M.S.), Division of Cardiac Surgery, Department of Surgery (T.A.), Division of Cardiovascular Medicine (T. N., E. C., Y.R.S., D.R., C.L.G., Q.S.W, R.J.G.), Department of Pharmacology and Department of Pathology, Immunology, and Microbiology (R.J.G.), Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Jay L
authors.initials: JL
authors.lastname: Zweier
authors.affiliation: From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine (D.M.R., C.M.S.), Division of Cardiac Surgery, Department of Surgery (T.A.), Division of Cardiovascular Medicine (T. N., E. C., Y.R.S., D.R., C.L.G., Q.S.W, R.J.G.), Department of Pharmacology and Department of Pathology, Immunology, and Microbiology (R.J.G.), Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Yanna
authors.initials: Y
authors.lastname: Song
authors.affiliation: From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine (D.M.R., C.M.S.), Division of Cardiac Surgery, Department of Surgery (T.A.), Division of Cardiovascular Medicine (T. N., E. C., Y.R.S., D.R., C.L.G., Q.S.W, R.J.G.), Department of Pharmacology and Department of Pathology, Immunology, and Microbiology (R.J.G.), Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Meng
authors.initials: M
authors.lastname: Xu
authors.affiliation: From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine (D.M.R., C.M.S.), Division of Cardiac Surgery, Department of Surgery (T.A.), Division of Cardiovascular Medicine (T. N., E. C., Y.R.S., D.R., C.L.G., Q.S.W, R.J.G.), Department of Pharmacology and Department of Pathology, Immunology, and Microbiology (R.J.G.), Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Frank E
authors.initials: FE
authors.lastname: Harrell
authors.affiliation: From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine (D.M.R., C.M.S.), Division of Cardiac Surgery, Department of Surgery (T.A.), Division of Cardiovascular Medicine (T. N., E. C., Y.R.S., D.R., C.L.G., Q.S.W, R.J.G.), Department of Pharmacology and Department of Pathology, Immunology, and Microbiology (R.J.G.), Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Yan Ru
authors.initials: YR
authors.lastname: Su
authors.affiliation: From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine (D.M.R., C.M.S.), Division of Cardiac Surgery, Department of Surgery (T.A.), Division of Cardiovascular Medicine (T. N., E. C., Y.R.S., D.R., C.L.G., Q.S.W, R.J.G.), Department of Pharmacology and Department of Pathology, Immunology, and Microbiology (R.J.G.), Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Tarek
authors.initials: T
authors.lastname: Absi
authors.affiliation: From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine (D.M.R., C.M.S.), Division of Cardiac Surgery, Department of Surgery (T.A.), Division of Cardiovascular Medicine (T. N., E. C., Y.R.S., D.R., C.L.G., Q.S.W, R.J.G.), Department of Pharmacology and Department of Pathology, Immunology, and Microbiology (R.J.G.), Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Kohr
authors.affiliation: From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine (D.M.R., C.M.S.), Division of Cardiac Surgery, Department of Surgery (T.A.), Division of Cardiovascular Medicine (T. N., E. C., Y.R.S., D.R., C.L.G., Q.S.W, R.J.G.), Department of Pharmacology and Department of Pathology, Immunology, and Microbiology (R.J.G.), Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Ziolo
authors.affiliation: From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine (D.M.R., C.M.S.), Division of Cardiac Surgery, Department of Surgery (T.A.), Division of Cardiovascular Medicine (T. N., E. C., Y.R.S., D.R., C.L.G., Q.S.W, R.J.G.), Department of Pharmacology and Department of Pathology, Immunology, and Microbiology (R.J.G.), Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Dan M
authors.initials: DM
authors.lastname: Roden
authors.affiliation: From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine (D.M.R., C.M.S.), Division of Cardiac Surgery, Department of Surgery (T.A.), Division of Cardiovascular Medicine (T. N., E. C., Y.R.S., D.R., C.L.G., Q.S.W, R.J.G.), Department of Pharmacology and Department of Pathology, Immunology, and Microbiology (R.J.G.), Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Shaffer
authors.affiliation: From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine (D.M.R., C.M.S.), Division of Cardiac Surgery, Department of Surgery (T.A.), Division of Cardiovascular Medicine (T. N., E. C., Y.R.S., D.R., C.L.G., Q.S.W, R.J.G.), Department of Pharmacology and Department of Pathology, Immunology, and Microbiology (R.J.G.), Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Cristi L
authors.initials: CL
authors.lastname: Galindo
authors.affiliation: From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine (D.M.R., C.M.S.), Division of Cardiac Surgery, Department of Surgery (T.A.), Division of Cardiovascular Medicine (T. N., E. C., Y.R.S., D.R., C.L.G., Q.S.W, R.J.G.), Department of Pharmacology and Department of Pathology, Immunology, and Microbiology (R.J.G.), Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Quinn S
authors.initials: QS
authors.lastname: Wells
authors.affiliation: From the Division of Cardiovascular Medicine, Davis Heart and Lung Research Institute (B.Z., D.G.W., Z.X., R.H., H.H., S.V., J.L.Z.), Department of Physiology and Cell Biology (B.Z., J.L.Z., M.J.K., M.T.Z.), The Ohio State University, Columbus; Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HuBei, China (B.Z.); Department of Biostatistics (Y.S., M.X., F.E.H.), Division of Clinical Pharmacology, Department of Medicine (D.M.R., C.M.S.), Division of Cardiac Surgery, Department of Surgery (T.A.), Division of Cardiovascular Medicine (T. N., E. C., Y.R.S., D.R., C.L.G., Q.S.W, R.J.G.), Department of Pharmacology and Department of Pathology, Immunology, and Microbiology (R.J.G.), Vanderbilt University Medical Center, Nashville, TN. richard.gumina@vanderbilt.edu.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Gumina
mesh_terms: D000328:Adult; D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000378:metabolism; D009202:Cardiomyopathies / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016022:Case-Control Studies; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress; D010641:Phenotype; D024661:Potassium Channels, Inwardly Rectifying / Q000172:deficiency* / Q000235:genetics; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000503:physiopathology; D016277:Ventricular Function, Left; D017725:Ventricular Pressure; D000099211:Phospholamban; D000099161:Kcnj11 Channel
chemical_list: D020746:Calcium Channels, L-Type; D002135:Calcium-Binding Proteins; D024661:Potassium Channels, Inwardly Rectifying; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D014443:Tyrosine; D000099211:Phospholamban; D000099161:Kcnj11 Channel; C002744:3-nitrotyrosine
keywords: KATP channels; calcium; calcium-binding proteins; reactive nitrogen species; sarcoplasmic reticulum calcium-transporting ATPases