ArticleThe Journal of general physiology2013
The G-protein-gated K+ channel, IKACh, is required for regulation of pacemaker activity and recovery of resting heart rate after sympathetic stimulation.
Article in The Journal of general physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 78 citations in OpenAlex.
- Autonomic imbalance in cardiovascular disease: molecular mechanisms and emerging therapeutics.American journal of physiology. Cell physiology · 2025Review
- Aging and sinus node dysfunction: mechanisms and future directions.Clinical science (London, England : 1979) · 2025Review
- Cardiac automaticity is modulated by IKACh in sinoatrial node during pregnancy.Cardiovascular research · 2024Article
- Modeling the atrioventricular conduction axis using human pluripotent stem cell-derived cardiac assembloids.Cell stem cell · 2024Article
- Pacemaker Channels and the Chronotropic Response in Health and Disease.Circulation research · 2024Review
- State-of-the-Art Differentiation Protocols for Patient-Derived Cardiac Pacemaker Cells.International journal of molecular sciences · 2024Review
- Increased GIRK channel activity prevents arrhythmia in mice with heart failure by enhancing ventricular repolarization.Scientific reports · 2023Article
- Lipopolysaccharide-induced sepsis impairs M2R-GIRK signaling in the mouse sinoatrial node.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Relevance ofInternational journal of molecular sciences · 2023Review
- Sinus node dysfunction: current understanding and future directions.American journal of physiology. Heart and circulatory physiology · 2023Review
- Heart rate reduction after genetic ablation of L-type CaFrontiers in cardiovascular medicine · 2023Article
- Autonomic nervous system and cardiac neuro-signaling pathway modulation in cardiovascular disorders and Alzheimer's disease.Frontiers in physiology · 2023Review
- Muscarinic acetylcholine receptors MFrontiers in cardiovascular medicine · 2023Article
- Paradigm shift: new concepts for HCN4 function in cardiac pacemaking.Pflugers Archiv : European journal of physiology · 2022Review
- Frequency-Dependent Properties of the Hyperpolarization-Activated Cation Current, IInternational journal of molecular sciences · 2022Article
- L-Type CaCells · 2022Article
- Characterization of VU0468554, a New Selective Inhibitor of Cardiac G Protein-Gated Inwardly Rectifying KMolecular pharmacology · 2021Article
- Impaired regulation of heart rate and sinoatrial node function by the parasympathetic nervous system in type 2 diabetic mice.Scientific reports · 2021Article
- Structural and Functional Properties of Subsidiary Atrial Pacemakers in a Goat Model of Sinus Node Disease.Frontiers in physiology · 2021Article
- Genetic Complexity of Sinoatrial Node Dysfunction.Frontiers in genetics · 2021Review
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Authors and funding
15 authors at 9 institutions in 3 countries.
Funding
Abstract
Parasympathetic regulation of sinoatrial node (SAN) pacemaker activity modulates multiple ion channels to temper heart rate. The functional role of the G-protein-activated K(+) current (IKACh) in the control of SAN pacemaking and heart rate is not completely understood. We have investigated the functional consequences of loss of IKACh in cholinergic regulation of pacemaker activity of SAN cells and in heart rate control under physiological situations mimicking the fight or flight response. We used knockout mice with loss of function of the Girk4 (Kir3.4) gene (Girk4(-/-) mice), which codes for an integral subunit of the cardiac IKACh channel. SAN pacemaker cells from Girk4(-/-) mice completely lacked IKACh. Loss of IKACh strongly reduced cholinergic regulation of pacemaker activity of SAN cells and isolated intact hearts. Telemetric recordings of electrocardiograms of freely moving mice showed that heart rate measured over a 24-h recording period was moderately increased (10%) in Girk4(-/-) animals. Although the relative extent of heart rate regulation of Girk4(-/-) mice was similar to that of wild-type animals, recovery of resting heart rate after stress, physical exercise, or pharmacological β-adrenergic stimulation of SAN pacemaking was significantly delayed in Girk4(-/-) animals. We conclude that IKACh plays a critical role in the kinetics of heart rate recovery to resting levels after sympathetic stimulation or after direct β-adrenergic stimulation of pacemaker activity. Our study thus uncovers a novel role for IKACh in SAN physiology and heart rate regulation.
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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.