ArticleThe Journal of biological chemistry2014
RGS6, but not RGS4, is the dominant regulator of G protein signaling (RGS) modulator of the parasympathetic regulation of mouse heart rate.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Genetic loci associated with heart rate variability and their effects on cardiac disease risk.Nature communications · 2017Pooled it
- G protein-gated inwardly rectifying KHistology and histopathology · 2025Review
- Rapid and accurate multi-phenotype imputation for millions of individuals.Nature communications · 2025Article
- The Role of KCells · 2024Review
- Cardiac RGS Proteins in Human Heart Failure and Atrial Fibrillation: Focus on RGS4.International journal of molecular sciences · 2023Review
- Neuronal G protein-gated KAmerican journal of physiology. Cell physiology · 2022Review
- 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
- Neurohumoral Control of Sinoatrial Node Activity and Heart Rate: Insight From Experimental Models and Findings From Humans.Frontiers in physiology · 2020Review
- Genetic variation inDisease models & mechanisms · 2019Article
- VU0810464, a non-urea G protein-gated inwardly rectifying KBritish journal of pharmacology · 2019Article
- Genetics and the heart rate response to exercise.Cellular and molecular life sciences : CMLS · 2019Review
- Genetic Analysis of Rare Human Variants of Regulators of G Protein Signaling Proteins and Their Role in Human Physiology and Disease.Pharmacological reviews · 2018Review
- Potential association of long noncoding RNA HA117 with tetralogy of Fallot.Genes & diseases · 2018Article
- Expression and relevance of the G protein-gated KScientific reports · 2018Article
- The agonist-specific voltage dependence of M2 muscarinic receptors modulates the deactivation of the acetylcholine-gated K(+) current (I KACh).Pflugers Archiv : European journal of physiology · 2016Article
- RGS proteins as targets in the treatment of intestinal inflammation and visceral pain: New insights and future perspectives.BioEssays : news and reviews in molecular, cellular and developmental biology · 2016Review
- From two competing oscillators to one coupled-clock pacemaker cell system.Frontiers in physiology · 2015Review
- The therapeutic potential of targeting cardiac RGS4.Therapeutic advances in cardiovascular diseaseReview
- Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Parasympathetic activity decreases heart rate (HR) by inhibiting pacemaker cells in the sinoatrial node (SAN). Dysregulation of parasympathetic influence has been linked to sinus node dysfunction and arrhythmia. RGS (regulator of G protein signaling) proteins are negative modulators of the parasympathetic regulation of HR and the prototypical M2 muscarinic receptor (M2R)-dependent signaling pathway in the SAN that involves the muscarinic-gated atrial K(+) channel IKACh. Both RGS4 and RGS6-Gβ5 have been implicated in these processes. Here, we used Rgs4(-/-), Rgs6(-/-), and Rgs4(-/-):Rgs6(-/-) mice to compare the relative influence of RGS4 and RGS6 on parasympathetic regulation of HR and M2R-IKACh-dependent signaling in the SAN. In retrogradely perfused hearts, ablation of RGS6, but not RGS4, correlated with decreased resting HR, increased heart rate variability, and enhanced sensitivity to the negative chronotropic effects of the muscarinic agonist carbachol. Similarly, loss of RGS6, but not RGS4, correlated with enhanced sensitivity of the M2R-IKACh signaling pathway in SAN cells to carbachol and a significant slowing of M2R-IKACh deactivation rate. Surprisingly, concurrent genetic ablation of RGS4 partially rescued some deficits observed in Rgs6(-/-) mice. These findings, together with those from an acute pharmacologic approach in SAN cells from Rgs6(-/-) and Gβ5(-/-) mice, suggest that the partial rescue of phenotypes in Rgs4(-/-):Rgs6(-/-) mice is attributable to another R7 RGS protein whose influence on M2R-IKACh signaling is masked by RGS4. Thus, RGS6-Gβ5, but not RGS4, is the primary RGS modulator of parasympathetic HR regulation and SAN M2R-IKACh signaling in mice.
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