ArticleJournal of molecular and cellular cardiology2009
Dysfunction of ouabain-induced cardiac contractility in mice with heart-specific ablation of Na,K-ATPase beta1-subunit.
Article in Journal of molecular and cellular cardiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 37 citations in OpenAlex.
- The mechanism of action of digoxin requires the sodium-dependent inactivation of the sodium-calcium exchanger.Science advances · 2025Article
- Identification and Functional Assessment of Candidate CausalCirculation. Genomic and precision medicine · 2025Article
- Role of NaInternational journal of molecular sciences · 2024Review
- Exosomal Preconditioning of Human iPSC-Derived Cardiomyocytes Beneficially Alters Cardiac Electrophysiology and Micro RNA Expression.International journal of molecular sciences · 2024Article
- Transcriptome and open chromatin analysis reveals the process of myocardial cell development and key pathogenic target proteins in Long QT syndrome type 7.Journal of translational medicine · 2024Article
- A proteomic analysis of atrial fibrillation in a prospective longitudinal cohort (AGES-Reykjavik study).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 · 2023Article
- Proteomics research of SARS-CoV-2 and COVID-19 disease.Medical review (2021) · 2022Review
- A Na,K-ATPase-Fodrin-Actin Membrane Cytoskeleton Complex is Required for Endothelial Fenestra Biogenesis.Cells · 2020Article
- Identification of putative biomarkers for Infantile Hemangiomas and Propranolol treatment via data integration.Scientific reports · 2020Article
- From Genome-Wide Association Studies to Cardiac Electrophysiology: Through the Maze of Biological Complexity.Frontiers in physiology · 2020Review
- The Structure and Function of the Na,K-ATPase Isoforms in Health and Disease.Frontiers in physiology · 2017Review
- Article
- Heritabilities, proportions of heritabilities explained by GWAS findings, and implications of cross-phenotype effects on PR interval.Human genetics · 2015Article
- Sodium-calcium exchanger 1 regulates epithelial cell migration via calcium-dependent extracellular signal-regulated kinase signaling.The Journal of biological chemistry · 2015Article
- Effects of exercise training on excitation-contraction coupling and related mRNA expression in hearts of Goto-Kakizaki type 2 diabetic rats.Molecular and cellular biochemistry · 2013Article
- A polymorphic 3'UTR element in ATP1B1 regulates alternative polyadenylation and is associated with blood pressure.PloS one · 2013Article
- Protective effects of Acyl-coA thioesterase 1 on diabetic heart via PPARα/PGC1α signaling.PloS one · 2012Article
- Cardiac electrophysiology in mice: a matter of size.Frontiers in physiology · 2012Article
- The emerging genetic landscape underlying cardiac conduction system function.Birth defects research. Part A, Clinical and molecular teratology · 2011Review
- High-frequency high-resolution echocardiography: first evidence on non-invasive repeated measure of myocardial strain, contractility, and mitral regurgitation in the ischemia-reperfused murine heart.Journal of visualized experiments : JoVE · 2010Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Na,K-ATPase is composed of two essential alpha- and beta-subunits, both of which have multiple isoforms. Evidence indicates that the Na,K-ATPase enzymatic activity as well as its alpha(1), alpha(3) and beta(1) isoforms are reduced in the failing human heart. The catalytic alpha-subunit is the receptor for cardiac glycosides such as digitalis, used for the treatment of congestive heart failure. The role of the Na,K-ATPase beta(1)-subunit (Na,K-beta(1)) in cardiac function is not known. We used Cre/loxP technology to inactivate the Na,K-beta(1) gene exclusively in the ventricular cardiomyocytes. Animals with homozygous Na,K-beta(1) gene excision were born at the expected Mendelian ratio, grew into adulthood, and appeared to be healthy until 10 months of age. At 13-14 months, these mice had 13% higher heart/body weight ratios, and reduced contractility as revealed by echocardiography compared to their wild-type (WT) littermates. Pressure overload by transverse aortic constriction (TAC) in younger mice, resulted in compensated hypertrophy in WT mice, but decompensation in the Na,K-beta(1) KO mice. The young KO survivors of TAC exhibited decreased contractile function and mimicked the effects of the Na,K-beta(1) KO in older mice. Further, we show that intact hearts of Na,K-beta(1) KO anesthetized mice as well as isolated cardiomyocytes were insensitive to ouabain-induced positive inotropy. This insensitivity was associated with a reduction in NCX1, one of the proteins involved in regulating cardiac contractility. In conclusion, our results demonstrate that Na,K-beta(1) plays an essential role in regulating cardiac contractility and that its loss is associated with significant pathophysiology of the heart.
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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.