ArticlePloS one2013
Essential role of the m2R-RGS6-IKACh pathway in controlling intrinsic heart rate variability.
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 28 papers, 1 of them a synthesis 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
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Genetic loci associated with heart rate variability and their effects on cardiac disease risk.Nature communications · 2017Pooled it
- Cardiac automaticity is modulated by IKACh in sinoatrial node during pregnancy.Cardiovascular research · 2024Article
- Article
- RGS6 drives cardiomyocyte death following nucleolar stress by suppressing Nucleolin/miRNA-21.Journal of translational medicine · 2024Article
- Gene expression in notochord and nuclei pulposi: a study of gene families across the chordate phylum.BMC ecology and evolution · 2023Article
- Phenotypic but not genetically predicted heart rate variability associated with all-cause mortality.Communications biology · 2023Article
- RGS7 balances acetylation/de-acetylation of p65 to control chemotherapy-dependent cardiac inflammation.Cellular and molecular life sciences : CMLS · 2023Article
- A RGS7-CaMKII complex drives myocyte-intrinsic and myocyte-extrinsic mechanisms of chemotherapy-induced cardiotoxicity.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Characterization of VU0468554, a New Selective Inhibitor of Cardiac G Protein-Gated Inwardly Rectifying KMolecular pharmacology · 2021Article
- Article
- Translating GWAS-identified loci for cardiac rhythm and rate using an in vivo image- and CRISPR/Cas9-based approach.Scientific reports · 2020Article
- GPCR-dependent biasing of GIRK channel signaling dynamics by RGS6 in mouse sinoatrial nodal cells.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- From Genome-Wide Association Studies to Cardiac Electrophysiology: Through the Maze of Biological Complexity.Frontiers in physiology · 2020Review
- Atypical activation of the G protein GαThe Journal of biological chemistry · 2018Article
- Differential effects of inhibitory G protein isoforms on G protein-gated inwardly rectifying KAmerican journal of physiology. Cell physiology · 2018Article
- HCN4 pacemaker channels attenuate the parasympathetic response and stabilize the spontaneous firing of the sinoatrial node.The Journal of physiology · 2018Article
- Expression and relevance of the G protein-gated KScientific reports · 2018Article
- Atrial GIRK Channels Mediate the Effects of Vagus Nerve Stimulation on Heart Rate Dynamics and Arrhythmogenesis.Frontiers in physiology · 2018Article
- The influences of the M2R-GIRK4-RGS6 dependent parasympathetic pathway on electrophysiological properties of the mouse heart.PloS one · 2018Article
- Regulator of G Protein Signaling 6 Protects the Heart from Ischemic Injury.The Journal of pharmacology and experimental therapeutics · 2017Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Normal heart function requires generation of a regular rhythm by sinoatrial pacemaker cells and the alteration of this spontaneous heart rate by the autonomic input to match physiological demand. However, the molecular mechanisms that ensure consistent periodicity of cardiac contractions and fine tuning of this process by autonomic system are not completely understood. Here we examined the contribution of the m2R-I(KACh) intracellular signaling pathway, which mediates the negative chronotropic effect of parasympathetic stimulation, to the regulation of the cardiac pacemaking rhythm. Using isolated heart preparations and single-cell recordings we show that the m2R-I(KACh) signaling pathway controls the excitability and firing pattern of the sinoatrial cardiomyocytes and determines variability of cardiac rhythm in a manner independent from the autonomic input. Ablation of the major regulator of this pathway, Rgs6, in mice results in irregular cardiac rhythmicity and increases susceptibility to atrial fibrillation. We further identify several human subjects with variants in the RGS6 gene and show that the loss of function in RGS6 correlates with increased heart rate variability. These findings identify the essential role of the m2R-I(KACh) signaling pathway in the regulation of cardiac sinus rhythm and implicate RGS6 in arrhythmia pathogenesis.
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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.