ArticleJournal of the American College of Cardiology2012
Cyclic adenosine monophosphate phosphodiesterase type 4 protects against atrial arrhythmias.
Article in Journal of the American College of Cardiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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68 citing papers in PubMed, 125 citations in OpenAlex.
- A modified method for isolation of human cardiomyocytes to model cardiac diseases.Journal of translational medicine · 2018Trial
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- Downregulation of L-type CaHeart rhythm · 2026Article
- Repurposed cAMP-Modulating Agents Enhance 5-Fluorouracil Response Through Membrane-Dependent Mechanisms.Membranes · 2026Review
- Cyclic AMP-dependent regulation of ryanodine receptors in healthy and diseased hearts.Journal of molecular and cellular cardiology · 2026Review
- Autonomic imbalance in cardiovascular disease: molecular mechanisms and emerging therapeutics.American journal of physiology. Cell physiology · 2025Review
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- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
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- Mechanisms of stretch-induced electro-anatomical remodeling and atrial arrhythmogenesis.Journal of molecular and cellular cardiology · 2024Review
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- PDE4D mediates impaired β-adrenergic receptor signalling in the sinoatrial node in mice with hypertensive heart disease.Cardiovascular research · 2023Article
- PDE4 Phosphodiesterases in Cardiovascular Diseases: Key Pathophysiological Players and Potential Therapeutic Targets.International journal of molecular sciences · 2023Review
- Caveolae-associated cAMP/CaJournal of molecular and cellular cardiology · 2023Article
- cAMP signaling affects age-associated deterioration of pacemaker beating interval dynamics.GeroScience · 2023Article
- Phosphodiesterase 8 governs cAMP/PKA-dependent reduction of L-type calcium current in human atrial fibrillation: a novel arrhythmogenic mechanism.European heart journal · 2023Article
- Compartmentalized cAMP signalling and control of cardiac rhythm.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Levosimendan increases the phosphorylation state of phospholamban in the isolated human atrium.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Expression and Impact of Adenosine AInternational journal of molecular sciences · 2023Article
- Serum Catestatin Concentrations Are Increased in Patients with Atrial Fibrillation.Journal of cardiovascular development and disease · 2023Article
8 more citing papers are in PubMed but not listed here.
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15 authors at 6 institutions in 5 countries.
Funding
Abstract
objectivesThis study was designed to examine whether a cyclic adenosine monophosphate (cAMP) phosphodiesterase (PDE), PDE4, is expressed in human atrium and contributes to the control of electrical stability.
backgroundAtrial fibrillation is accompanied by a profound remodeling of membrane receptors and alterations in cAMP-dependent regulation of Ca(2+) handling. Being responsible for cAMP hydrolysis, PDEs are likely to play a role in this setting. In the rodent heart, PDE4 contributes up to 60% of total cAMP-hydrolytic activity. However, its role in the human heart remains controversial.
methodsL-type Ca(2+) current and spontaneous Ca(2+) release were recorded in isolated human atrial myocytes. Intracellular cAMP was measured by live cell imaging using a fluorescence resonance energy transfer-based sensor. Contractile force and arrhythmias were recorded in human atrial trabeculae. PDE activity was measured in human atrial tissue from patients in sinus rhythm and permanent atrial fibrillation.
resultsPDE4 is expressed in human atrial myocytes and accounts for approximately 15% of total PDE activity. PDE4D represents the major PDE4 subtype. PDE4 inhibition increased intracellular cAMP and L-type Ca(2+) current and dramatically delayed their decay after a brief β-adrenergic stimulation. PDE4 inhibition also increased the frequency of spontaneous Ca(2+) release at baseline, as well as the contractile response and the incidence of arrhythmias in human atrial strips during β-adrenergic stimulation. Total PDE activity decreased with age, and the relative PDE4 activity was lower in patients with permanent atrial fibrillation than in age-matched sinus rhythm controls.
conclusionsPDE4 is critical in controlling cAMP levels and thereby Ca(2+) influx and release in human atrial muscle, hence limiting the susceptibility to arrhythmias.
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