ArticlePloS one2013
ß-Adrenergic stimulation increases RyR2 activity via intracellular Ca2+ and Mg2+ regulation.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- The association of serum magnesium and mortality outcomes in heart failure patients: A systematic review and meta-analysis.Medicine · 2016Pooled it
- βNaunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Review
- Structure-based mechanism of RyR channel operation by calcium and magnesium ions.PLoS computational biology · 2025Article
- Phosphorylation of phospholamban promotes SERCA2a activation by dwarf open reading frame (DWORF).Cell calcium · 2024Article
- Roles of β-adrenoceptor Subtypes and Therapeutics in Human Cardiovascular Disease: Heart Failure, Tachyarrhythmias and Other Cardiovascular Disorders.Handbook of experimental pharmacology · 2024Review
- Hypermagnesemia in Clinical Practice.Medicina (Kaunas, Lithuania) · 2023Review
- Targeting p21-activated kinase 1 for development of a novel anti-arrhythmic drug class.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Increased Mitochondrial Calcium Fluxes in Hypertrophic Right Ventricular Cardiomyocytes from a Rat Model of Pulmonary Artery Hypertension.Life (Basel, Switzerland) · 2023Article
- Structural analyses of human ryanodine receptor type 2 channels reveal the mechanisms for sudden cardiac death and treatment.Science advances · 2022Article
- Hypermagnesaemia, but Not Hypomagnesaemia, Is a Predictor of Inpatient Mortality in Critically Ill Children with Sepsis.Disease markers · 2022Article
- Integrated Quantitative Phosphoproteomics and Cell-based Functional Screening Reveals Specific Pathological Cardiac Hypertrophy-related Phosphorylation Sites.Molecules and cells · 2021Article
- RYR2 Channel Inhibition Is the Principal Mechanism of Flecainide Action in CPVT.Circulation research · 2021Article
- High-Normal Serum Magnesium and Hypermagnesemia Are Associated With Increased 30-Day In-Hospital Mortality: A Retrospective Cohort Study.Frontiers in cardiovascular medicine · 2021Article
- Magnesium Ions Moderate Calcium-Induced Calcium Release in Cardiac Calcium Release Sites by Binding to Ryanodine Receptor Activation and Inhibition Sites.Frontiers in physiology · 2021Article
- Multisite phosphorylation of the cardiac ryanodine receptor: a random or coordinated event?Pflugers Archiv : European journal of physiology · 2020Review
- Autonomous activation of CaMKII exacerbates diastolic calcium leak during beta-adrenergic stimulation in cardiomyocytes of metabolic syndrome rats.Cell calcium · 2020Article
- Ion channel gating in cardiac ryanodine receptors from the arrhythmic RyR2-P2328S mouse.Journal of cell science · 2019Article
- Calmodulin inhibition of human RyR2 channels requires phosphorylation of RyR2-S2808 or RyR2-S2814.Journal of molecular and cellular cardiology · 2019Article
- Three-Dimensional and Chemical Mapping of Intracellular Signaling Nanodomains in Health and Disease with Enhanced Expansion Microscopy.ACS nano · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Here we investigate how ß-adrenergic stimulation of the heart alters regulation of ryanodine receptors (RyRs) by intracellular Ca(2+) and Mg(2+) and the role of these changes in SR Ca(2+) release. RyRs were isolated from rat hearts, perfused in a Langendorff apparatus for 5 min and subject to 1 min perfusion with 1 µM isoproterenol or without (control) and snap frozen in liquid N2 to capture their phosphorylation state. Western Blots show that RyR2 phosphorylation was increased by isoproterenol, confirming that RyR2 were subject to normal ß-adrenergic signaling. Under basal conditions, S2808 and S2814 had phosphorylation levels of 69% and 15%, respectively. These levels were increased to 83% and 60%, respectively, after 60 s of ß-adrenergic stimulation consistent with other reports that ß-adrenergic stimulation of the heart can phosphorylate RyRs at specific residues including S2808 and S2814 causing an increase in RyR activity. At cytoplasmic [Ca(2+)] <1 µM, ß-adrenergic stimulation increased luminal Ca(2+) activation of single RyR channels, decreased luminal Mg(2+) inhibition and decreased inhibition of RyRs by mM cytoplasmic Mg(2+). At cytoplasmic [Ca(2+)] >1 µM, ß-adrenergic stimulation only decreased cytoplasmic Mg(2+) and Ca(2+) inhibition of RyRs. The Ka and maximum levels of cytoplasmic Ca(2+) activation site were not affected by ß-adrenergic stimulation. Our RyR2 gating model was fitted to the single channel data. It predicted that in diastole, ß-adrenergic stimulation is mediated by 1) increasing the activating potency of Ca(2+) binding to the luminal Ca(2+) site and decreasing its affinity for luminal Mg(2+) and 2) decreasing affinity of the low-affinity Ca(2+)/Mg(2+) cytoplasmic inhibition site. However in systole, ß-adrenergic stimulation is mediated mainly by the latter.
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