ArticleCirculation2008
Phospholemman-mediated activation of Na/K-ATPase limits [Na]i and inotropic state during beta-adrenergic stimulation in mouse ventricular myocytes.
Article in Circulation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed.
- Dynamic visualization of physiological CaMKII activity using sensitive FRET biosensors.bioRxiv : the preprint server for biology · 2026Article
- A model of β-adrenergic stimulation in human ventricular cells for tissue-scale simulations of sympathetically modulated tachycardias.The Journal of physiology · 2026Article
- Post-translational modifications of na+/K+-atpase subunits: regulatory mechanisms and functional implications.Frontiers in cell and developmental biology · 2026Review
- Protein palmitoylation: A potential therapeutic target in cardiovascular diseases.Acta pharmaceutica Sinica. B · 2025Review
- Role of NaInternational journal of molecular sciences · 2024Review
- A new approach to characterize cardiac sodium storage by combining fluorescence photometry and magnetic resonance imaging in small animal research.Scientific reports · 2024Article
- The zebrafish mutanteLife · 2023Article
- Compartmentalized cAMP signalling and control of cardiac rhythm.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- NaCirculation research · 2022Article
- Regulation of Cardiac Contractility by the Alpha 2 Subunit of the NaFrontiers in physiology · 2022Review
- Article
- Intracellular NaInternational journal of molecular sciences · 2021Article
- Phospholemman Phosphorylation Regulates Vascular Tone, Blood Pressure, and Hypertension in Mice and Humans.Circulation · 2021Article
- Whole-Cell cAMP and PKA Activity are Epiphenomena, Nanodomain Signaling Matters.Physiology (Bethesda, Md.) · 2019Review
- Heart failure leads to altered β2-adrenoceptor/cyclic adenosine monophosphate dynamics in the sarcolemmal phospholemman/Na,K ATPase microdomain.Cardiovascular research · 2019Article
- Hypokalemia-Induced Arrhythmias and Heart Failure: New Insights and Implications for Therapy.Frontiers in physiology · 2018Review
- Over-expression of microRNA-1 causes arrhythmia by disturbing intracellular trafficking system.Scientific reports · 2017Article
- A Simplified, Langendorff-Free Method for Concomitant Isolation of Viable Cardiac Myocytes and Nonmyocytes From the Adult Mouse Heart.Circulation research · 2016Article
- Development of a high-affinity peptide that prevents phospholemman (PLM) inhibition of the sodium/calcium exchanger 1 (NCX1).The Biochemical journal · 2016Article
- Article
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3 authors.
Funding
Abstract
backgroundCardiac Na/K-ATPase (NKA) regulates intracellular Na ([Na](i)), which in turn affects intracellular Ca and thus contractility via Na/Ca exchange. Recent evidence shows that phosphorylation of the NKA-associated small transmembrane protein phospholemman (PLM) mediates beta-adrenergic-induced NKA stimulation. METHODS AND
resultsHere, we tested whether PLM phosphorylation during beta-adrenergic activation limits the rise in [Na](i), Ca transient amplitude, and triggered arrhythmias in mouse ventricular myocytes. In myocytes from wild-type (WT) mice, [Na](i) increased on field stimulation at 2 Hz from 11.1+/-1.8 mmol/L to a plateau of 15.2+/-1.5 mmol/L. Isoproterenol induced a decrease in [Na](i) to 12.0+/-1.2 mmol/L. In PLM knockout (PLM-KO) mice in which beta-adrenergic stimulation does not activate NKA, [Na](i) also increased at 2 Hz (from 10.4+/-1.2 to 17.0+/-1.5 mmol/L) but was unaltered by isoproterenol. The PLM-mediated decrease in [Na](i) in WT mice could limit the isoproterenol-induced inotropic state. Indeed, the isoproterenol-induced increase in the amplitude of Ca transients was significantly smaller in the WT mice (5.2+/-0.4- versus 7.1+/-0.5-fold in PLM-KO mice). This also was the case for the sarcoplasmic reticulum Ca content, which increased by 1.27+/-0.09-fold in WT mice versus 1.53+/-0.09-fold in PLM-KO mice. The higher sarcoplasmic reticulum Ca content in PLM-KO versus WT mice was associated with an increased propensity for spontaneous Ca transients and contractions in PLM-KO mice.
conclusionsThese data suggest that PLM phosphorylation and NKA stimulation are an integral part of the sympathetic fight-or-flight response, tempering the rise in [Na](i) and cellular Ca loading and perhaps limiting Ca overload-induced arrhythmias.
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