ArticleCirculation research2008
RGS4 regulates parasympathetic signaling and heart rate control in the sinoatrial node.
Article in Circulation research, 2008. 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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Who cites it
68 citing papers in PubMed, 131 citations in OpenAlex.
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- An optimized Langendorff-free isolating method and electrophysiology studies for adult mouse atrioventricular node cells.BMC cardiovascular disorders · 2025Article
- An endogenous cholinergic system controls electrical conduction in the heart.European heart journal · 2025Article
- G protein regulation by RGS proteins in the pathophysiology of dilated cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2025Review
- Cardiac automaticity is modulated by IKACh in sinoatrial node during pregnancy.Cardiovascular research · 2024Article
- Exploring the impact of electrocardiographic parameters on the risk of common arrhythmias: a two-sample Mendelian randomization study.Journal of thoracic disease · 2024Article
- The Role of KCells · 2024Review
- Direct modulation of G protein-gated inwardly rectifying potassium (GIRK) channels.Frontiers in physiology · 2024Review
- Cardiac RGS Proteins in Human Heart Failure and Atrial Fibrillation: Focus on RGS4.International journal of molecular sciences · 2023Review
- The AP-1 transcription factor Fosl-2 drives cardiac fibrosis and arrhythmias under immunofibrotic conditions.Communications biology · 2023Article
- Autonomic Nervous System Regulation of Epicardial Adipose Tissue: Potential Roles for Regulator of G Protein Signaling-4.Current issues in molecular biology · 2022Review
- The Relevance of GIRK Channels in Heart Function.Membranes · 2022Review
- Regulator of G-Protein Signaling-4 Attenuates Cardiac Adverse Remodeling and Neuronal Norepinephrine Release-Promoting Free Fatty Acid Receptor FFAR3 Signaling.International journal of molecular sciences · 2022Article
- Structural and Electrical Remodeling of the Sinoatrial Node in Diabetes: New Dimensions and Perspectives.Frontiers in endocrinology · 2022Review
- RGS4-Deficiency Alters Intracellular Calcium and PKA-Mediated Control of Insulin Secretion in Glucose-Stimulated Beta Islets.Biomedicines · 2021Article
- Selection of safe artemisinin derivatives using a machine learning-based cardiotoxicity platform and in vitro and in vivo validation.Archives of toxicology · 2021Article
- Impaired regulation of heart rate and sinoatrial node function by the parasympathetic nervous system in type 2 diabetic mice.Scientific reports · 2021Article
- cAMP-dependent regulation of HCN4 controls the tonic entrainment process in sinoatrial node pacemaker cells.Nature communications · 2020Article
- Neurohumoral Control of Sinoatrial Node Activity and Heart Rate: Insight From Experimental Models and Findings From Humans.Frontiers in physiology · 2020Review
- Interplay of cysteine exposure and global protein dynamics in small-molecule recognition by a regulator of G-protein signaling protein.Proteins · 2019Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heart rate is controlled by the opposing activities of sympathetic and parasympathetic inputs to pacemaker myocytes in the sinoatrial node (SAN). Parasympathetic activity on nodal myocytes is mediated by acetylcholine-dependent stimulation of M(2) muscarinic receptors and activation of Galpha(i/o) signaling. Although regulators of G protein signaling (RGS) proteins are potent inhibitors of Galpha(i/o) signaling in many tissues, the RGS protein(s) that regulate parasympathetic tone in the SAN are unknown. Our results demonstrate that RGS4 mRNA levels are higher in the SAN compared to right atrium. Conscious freely moving RGS4-null mice showed increased bradycardic responses to parasympathetic agonists compared to wild-type animals. Moreover, anesthetized RGS4-null mice had lower baseline heart rates and greater heart rate increases following atropine administration. Retrograde-perfused hearts from RGS4-null mice showed enhanced negative chronotropic responses to carbachol, whereas SAN myocytes showed greater sensitivity to carbachol-mediated reduction in the action potential firing rate. Finally, RGS4-null SAN cells showed decreased levels of G protein-coupled inward rectifying potassium (GIRK) channel desensitization and altered modulation of acetylcholine-sensitive potassium current (I(KACh)) kinetics following carbachol stimulation. Taken together, our studies establish that RGS4 plays an important role in regulating sinus rhythm by inhibiting parasympathetic signaling and I(KACh) activity.
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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.