ArticleCirculation2012
Cardiac G-protein-coupled receptor kinase 2 ablation induces a novel Ca2+ handling phenotype resistant to adverse alterations and remodeling after myocardial infarction.
Article in Circulation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
29 citing papers in PubMed, 40 citations in OpenAlex.
- miR-181a post-transcriptionally targets GRK2 to limit maladaptive signaling in cardiomyocytes.Frontiers in cardiovascular medicine · 2026Article
- GRK2 and Mitochondrial Dynamics in Cardiovascular Health and Disease.International journal of molecular sciences · 2025Review
- Unraveling the RKIP-YY1 axis: immune crosstalk in the pathogenesis of metabolic disorders.Frontiers in immunology · 2025Review
- Unheralded Adrenergic Receptor Signaling in Cellular Oxidative Stress and Death.Current opinion in physiology · 2024Article
- Tandem Mass Tagging Based Identification of Proteome Signatures for Reductive Stress Cardiomyopathy.Frontiers in cardiovascular medicine · 2022Article
- Functional resilience of C57BL/6J mouse heart to dietary fat overload.American journal of physiology. Heart and circulatory physiology · 2021Article
- Review
- Paroxetine Attenuates Cardiac Hypertrophy Via Blocking GRK2 and ADRB1 Interaction in Hypertension.Journal of the American Heart Association · 2021Article
- Cardiac myocyte KLF5 regulates body weight via alteration of cardiac FGF21.Biochimica et biophysica acta. Molecular basis of disease · 2019Article
- Myocardial-restricted ablation of the GTPase RAD results in a pro-adaptive heart response in mice.The Journal of biological chemistry · 2019Article
- GRKs and β-Arrestins: "Gatekeepers" of Mitochondrial Function in the Failing Heart.Frontiers in pharmacology · 2019Review
- Restricting mitochondrial GRK2 post-ischemia confers cardioprotection by reducing myocyte death and maintaining glucose oxidation.Science signaling · 2018Article
- Rad GTPase deletion attenuates post-ischemic cardiac dysfunction and remodeling.JACC. Basic to translational science · 2018Article
- Adverse Effects on β-Adrenergic Receptor Coupling: Ischemic Postconditioning Failed to Preserve Long-Term Cardiac Function.Journal of the American Heart Association · 2017Article
- Transgenic overexpression of GTP cyclohydrolase 1 in cardiomyocytes ameliorates post-infarction cardiac remodeling.Scientific reports · 2017Article
- Article
- Skeletal Muscle-specific G Protein-coupled Receptor Kinase 2 Ablation Alters Isolated Skeletal Muscle Mechanics and Enhances Clenbuterol-stimulated Hypertrophy.The Journal of biological chemistry · 2016Article
- The expanding GRK interactome: Implications in cardiovascular disease and potential for therapeutic development.Pharmacological research · 2016Review
- Molecular Mechanisms of Sympathetic Remodeling and Arrhythmias.Circulation. Arrhythmia and electrophysiology · 2016Review
- The nervous heart.Progress in biophysics and molecular biology · 2016Review
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundG-protein-coupled receptor kinase 2 (GRK2) is a primary regulator of β-adrenergic signaling in the heart. G-protein-coupled receptor kinase 2 ablation impedes heart failure development, but elucidation of the cellular mechanisms has not been achieved, and such elucidation is the aim of this study. METHODS AND
resultsMyocyte contractility, Ca(2+) handling and excitation-contraction coupling were studied in isolated cardiomyocytes from wild-type and GRK2 knockout (GRK2KO) mice without (sham) or with myocardial infarction (MI). In cardiac myocytes isolated from unstressed wild-type and GRK2KO hearts, myocyte contractions and Ca(2+) transients were similar, but GRK2KO myocytes had lower sarcoplasmic reticulum (SR) Ca(2+) content because of increased sodium-Ca(2+) exchanger activity and inhibited SR Ca(2+) ATPase by local protein kinase A-mediated activation of phosphodiesterase 4 resulting in hypophosphorylated phospholamban. This Ca(2+) handling phenotype is explained by a higher fractional SR Ca(2+) release induced by increased L-type Ca(2+) channel currents. After β-adrenergic stimulation, GRK2KO myocytes revealed significant increases in contractility and Ca(2+) transients, which were not mediated through cardiac L-type Ca(2+) channels but through an increased SR Ca(2+). Interestingly, post-MI GRK2KO mice showed better cardiac function than post-MI control mice, which is explained by an improved Ca(2+) handling phenotype. The SR Ca(2+) content was better maintained in post-MI GRK2KO myocytes than in post-MI control myocytes because of better-maintained L-type Ca(2+) channel current density and no increase in sodium-Ca(2+) exchanger in GRK2KO myocytes. An L-type Ca(2+) channel blocker, verapamil, reversed some beneficial effects of GRK2KO.
conclusionsThese data argue for novel differential regulation of L-type Ca(2+) channel currents and SR load by GRK2. G-protein-coupled receptor kinase 2 ablation represents a novel beneficial Ca(2+) handling phenotype resisting adverse remodeling after MI.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.