ArticleCirculation research2009
miR-1 overexpression enhances Ca(2+) release and promotes cardiac arrhythmogenesis by targeting PP2A regulatory subunit B56alpha and causing CaMKII-dependent hyperphosphorylation of RyR2.
Article in Circulation research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers, 2 of them syntheses that pooled it.
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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
132 citing papers in PubMed, 2 syntheses or guidelines pooled it, 279 citations in OpenAlex.
- Progress in research on the role of exosomal miRNAs in the diagnosis and treatment of cardiovascular diseases.Frontiers in genetics · 2022Pooled it
- MicroRNAs in Atrial Fibrillation: from Expression Signatures to Functional Implications.Cardiovascular drugs and therapy · 2017Pooled it
- Functional prediction of miR-3144-5p in human cardiac myocytes based on transcriptome sequencing and bioinformatics.Medicine · 2017Trial
- Impact ofJournal of cardiovascular development and disease · 2026Review
- Kinase regulation of miRNA networks in cardiometabolic disease: emerging pathways to precision therapy.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Emerging roles of microRNAs and other non-coding transcriptome in muscular dystrophies.Inflammation and regeneration · 2026Review
- Exosomal mir-126-3p derived from endothelial cells induces ion channel dysfunction by targeting RGS3 signaling in cardiomyocytes: a novel mechanism in Takotsubo cardiomyopathy.Stem cell research & therapy · 2025Article
- MicroRNAs in atrial fibrillation - have we discovered the Holy Grail or opened a Pandora's box?Frontiers in pharmacology · 2025Review
- Exosomal Preconditioning of Human iPSC-Derived Cardiomyocytes Beneficially Alters Cardiac Electrophysiology and Micro RNA Expression.International journal of molecular sciences · 2024Article
- Non-Coding RNA-Mediated Gene Regulation in Cardiovascular Disorders: Current Insights and Future Directions.Journal of cardiovascular translational research · 2024Review
- Abnormal phosphorylation / dephosphorylation and CaHeart failure reviews · 2024Review
- Loss of protein phosphatase 2A regulatory subunitFrontiers in cardiovascular medicine · 2024Article
- MicroRNA-1 Deficiency Is a Primary Etiological Factor Disrupting Cardiac Contractility and Electrophysiological Homeostasis.Circulation. Arrhythmia and electrophysiology · 2024Article
- Potential Roles of microRNAs for Assessing Cardiovascular Risk in Pre-Eclampsia-Exposed Postpartum Women and Offspring.International journal of molecular sciences · 2023Review
- The role of miR1 and miR133a in new-onset atrial fibrillation after acute myocardial infarction.BMC cardiovascular disorders · 2023Article
- 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
- The potential of using non-coding RNAs in forensic science applications.Forensic sciences research · 2023Review
- Non-coding RNA and arrhythmias: expression, function, and molecular mechanism.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 · 2023Review
- Dysregulated Cell Homeostasis and miRNAs in Human iPSC-Derived Cardiomyocytes from a Propionic Acidemia Patient with Cardiomyopathy.International journal of molecular sciences · 2023Article
- MicroRNAs in Dystrophinopathy.International journal of molecular sciences · 2022Review
72 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
MicroRNAs are small endogenous noncoding RNAs that regulate protein expression by hybridization to imprecise complementary sequences of target mRNAs. Changes in abundance of muscle-specific microRNA, miR-1, have been implicated in cardiac disease, including arrhythmia and heart failure. However, the specific molecular targets and cellular mechanisms involved in the action of miR-1 in the heart are only beginning to emerge. In this study we investigated the effects of increased expression of miR-1 on excitation-contraction coupling and Ca(2+) cycling in rat ventricular myocytes using methods of electrophysiology, Ca(2+) imaging and quantitative immunoblotting. Adenoviral-mediated overexpression of miR-1 in myocytes resulted in a marked increase in the amplitude of the inward Ca(2+) current, flattening of Ca(2+) transients voltage dependence, and enhanced frequency of spontaneous Ca(2+) sparks while reducing the sarcoplasmic reticulum Ca(2+) content as compared with control. In the presence of isoproterenol, rhythmically paced, miR-1-overexpressing myocytes exhibited spontaneous arrhythmogenic oscillations of intracellular Ca(2+), events that occurred rarely in control myocytes under the same conditions. The effects of miR-1 were completely reversed by the CaMKII inhibitor KN93. Although phosphorylation of phospholamban was not altered, miR-1 overexpression increased phosphorylation of the ryanodine receptor (RyR2) at S2814 (Ca(2+)/calmodulin-dependent protein kinase) but not at S2808 (protein kinase A). Overexpression of miR-1 was accompanied by a selective decrease in expression of the protein phosphatase PP2A regulatory subunit B56alpha involved in PP2A targeting to specialized subcellular domains. We conclude that miR-1 enhances cardiac excitation-contraction coupling by selectively increasing phosphorylation of the L-type and RyR2 channels via disrupting localization of PP2A activity to these channels.
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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.