ArticleProceedings of the National Academy of Sciences of the United States of America2009
The cAMP binding protein Epac regulates cardiac myofilament function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 85 citations in OpenAlex.
- Epac1 increases myosin regulatory light-chain phosphorylation, energetic cost of contraction, and susceptibility to heart failure.PloS one · 2025Article
- Article
- Differential changes in cyclic adenosine 3'-5' monophosphate (cAMP) effectors and major CaJournal of cellular and molecular medicine · 2023Article
- Cardioprotection of Immature Heart by Simultaneous Activation of PKA and Epac: A Role for the Mitochondrial Permeability Transition Pore.International journal of molecular sciences · 2022Article
- Adhesion G protein-coupled receptor Gpr126/Adgrg6 is essential for placental development.Science advances · 2021Article
- Subcellular Organization of the cAMP Signaling Pathway.Pharmacological reviews · 2021Review
- Phospho-substrate profiling of Epac-dependent protein kinase C activity.Molecular and cellular biochemistry · 2019Article
- Role of β-adrenergic signaling in masseter muscle.PloS one · 2019Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Epac Function and cAMP Scaffolds in the Heart and Lung.Journal of cardiovascular development and disease · 2018Review
- Epac activation inhibits IL-6-induced cardiac myocyte dysfunction.The journal of physiological sciences : JPS · 2018Article
- Diabetic Cardiomyopathy: Current and Future Therapies. Beyond Glycemic Control.Frontiers in physiology · 2018Review
- Early effects of Epac depend on the fine-tuning of the sarcoplasmic reticulum CaJournal of molecular and cellular cardiology · 2018Article
- Structure-activity relationships of 2-substituted phenyl-N-phenyl-2-oxoacetohydrazonoyl cyanides as novel antagonists of exchange proteins directly activated by cAMP (EPACs).Bioorganic & medicinal chemistry letters · 2017Article
- Increased passive stiffness promotes diastolic dysfunction despite improved Ca2+ handling during left ventricular concentric hypertrophy.Cardiovascular research · 2017Article
- Functional and cardioprotective effects of simultaneous and individual activation of protein kinase A and Epac.British journal of pharmacology · 2017Article
- The role of Epac in the heart.Cellular and molecular life sciences : CMLS · 2017Review
- New Antihyperglycemic Drugs and Heart Failure: Synopsis of Basic and Clinical Data.BioMed research international · 2017Review
- Inhibition of Epac1 suppresses mitochondrial fission and reduces neointima formation induced by vascular injury.Scientific reports · 2016Article
- Long-term consumption of an obesogenic high fat diet prior to ischemia-reperfusion mediates cardioprotection via Epac1-dependent signaling.Nutrition & metabolism · 2016Article
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the heart, cAMP is a key regulator of excitation-contraction coupling and its biological effects are mainly associated with the activity of protein kinase A (PKA). The aim of this study was to investigate the contribution of the cAMP-binding protein Epac (Exchange protein directly activated by cAMP) in the regulation of the contractile properties of rat ventricular cardiac myocytes. We report that both PKA and Epac increased cardiac sarcomere contraction but through opposite mechanisms. Differently from PKA, selective Epac activation by the cAMP analog 8-(4-chlorophenylthio)-2'-O-methyl-cAMP (8-pCPT) reduced Ca(2+) transient amplitude and increased cell shortening in intact cardiomyocytes and myofilament Ca(2+) sensitivity in permeabilized cardiomyocytes. Moreover, ventricular myocytes, which were infected in vivo with a constitutively active form of Epac, showed enhanced myofilament Ca(2+) sensitivity compared to control cells infected with green fluorescent protein (GFP) alone. At the molecular level, Epac increased phosphorylation of 2 key sarcomeric proteins, cardiac Troponin I (cTnI) and cardiac Myosin Binding Protein-C (cMyBP-C). The effects of Epac activation on myofilament Ca(2+) sensitivity and on cTnI and cMyBP-C phosphorylation were independent of PKA and were blocked by protein kinase C (PKC) and Ca(2+) calmodulin kinase II (CaMKII) inhibitors. Altogether these findings identify Epac as a new regulator of myofilament function.
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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.