ArticleJournal of molecular and cellular cardiology2013
Nitric oxide regulates cardiac intracellular Na⁺ and Ca²⁺ by modulating Na/K ATPase via PKCε and phospholemman-dependent mechanism.
Article in Journal of molecular and cellular cardiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 45 citations in OpenAlex.
- Intensive training and reduced volume increases muscle FXYD1 expression and phosphorylation at rest and during exercise in athletes.American journal of physiology. Regulatory, integrative and comparative physiology · 2016Trial
- The role of Na,K‑ATPase in lung diseases (Review).Molecular medicine reports · 2025Review
- FXYD proteins and sodium pump regulatory mechanisms.The Journal of general physiology · 2021Review
- Phospholemman Phosphorylation Regulates Vascular Tone, Blood Pressure, and Hypertension in Mice and Humans.Circulation · 2021Article
- Fibroblast Growth Factor 1 Reduces Pulmonary Vein and Atrium ArrhythmogenesisFrontiers in cardiovascular medicine · 2021Article
- Endogenous cardiotonic steroids and cardiovascular disease, where to next?Cell calcium · 2020Review
- Cytoprotective Effects of Dinitrosyl Iron Complexes on Viability of Human Fibroblasts and Cardiomyocytes.Frontiers in pharmacology · 2019Article
- Hypokalemia-Induced Arrhythmias and Heart Failure: New Insights and Implications for Therapy.Frontiers in physiology · 2018Review
- A role of the sodium pump in spreading ischemia in rats.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Article
- Serine/Threonine Phosphatases in Atrial Fibrillation.Journal of molecular and cellular cardiology · 2017Review
- Novel Sulfur Metabolites of Garlic Attenuate Cardiac Hypertrophy and Remodeling through Induction of NaFrontiers in pharmacology · 2017Article
- Pivotal role of α2 NaThe Journal of physiology · 2016Review
- "Oxygen Sensing" by Na,K-ATPase: These Miraculous Thiols.Frontiers in physiology · 2016Review
- Na+/Ca2+ exchange and Na+/K+-ATPase in the heart.The Journal of physiology · 2015Review
- Abnormal Ca(2+) cycling in failing ventricular myocytes: role of NOS1-mediated nitroso-redox balance.Antioxidants & redox signaling · 2014Review
- Cardiac hypertrophy in mice expressing unphosphorylatable phospholemman.Cardiovascular research · 2014Article
- Nitric oxide, vasodilation and the red blood cell.Biorheology · 2014Review
- Article
- Exercise training enhances multiple mechanisms of relaxation in coronary arteries from ischemic hearts.American journal of physiology. Heart and circulatory physiology · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
In the heart, Na/K-ATPase regulates intracellular Na(+) and Ca(2+) (via NCX), thereby preventing Na(+) and Ca(2+) overload and arrhythmias. Here, we test the hypothesis that nitric oxide (NO) regulates cardiac intracellular Na(+) and Ca(2+) and investigate mechanisms and physiological consequences involved. Effects of both exogenous NO (via NO-donors) and endogenously synthesized NO (via field-stimulation of ventricular myocytes) were assessed in this study. Field stimulation of rat ventricular myocytes significantly increased endogenous NO (18 ± 2 μM), PKCε activation (82 ± 12%), phospholemman phosphorylation (at Ser-63 and Ser-68) and Na/K-ATPase activity (measured by DAF-FM dye, western-blotting and biochemical assay, respectively; p<0.05, n=6) and all were abolished by Ca(2+)-chelation (EGTA 10mM) or NOS inhibition l-NAME (1mM). Exogenously added NO (spermine-NONO-ate) stimulated Na/K-ATPase (EC50=3.8 μM; n=6/grp), via decrease in Km, in PLM(WT) but not PLM(KO) or PLM(3SA) myocytes (where phospholemman cannot be phosphorylated) as measured by whole-cell perforated-patch clamp. Field-stimulation with l-NAME or PKC-inhibitor (2 μM Bis) resulted in elevated intracellular Na(+) (22 ± 1.5 and 24 ± 2 respectively, vs. 14 ± 0.6mM in controls) in SBFI-AM-loaded rat myocytes. Arrhythmia incidence was significantly increased in rat hearts paced in the presence of l-NAME (and this was reversed by l-arginine), as well as in PLM(3SA) mouse hearts but not PLM(WT) and PLM(KO). We provide physiological and biochemical evidence for a novel regulatory pathway whereby NO activates Na/K-ATPase via phospholemman phosphorylation and thereby limits Na(+) and Ca(2+) overload and arrhythmias. This article is part of a Special Issue entitled "Na(+) Regulation in Cardiac Myocytes".
Indexed as
Identifiers
What OpenQuestion holds
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.