ArticleNature communications2020
cAMP-dependent regulation of HCN4 controls the tonic entrainment process in sinoatrial node pacemaker cells.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 82 citations in OpenAlex.
- Cardiac Pacemaker Cells Harness Stochastic Resonance to Avoid Sinus Arrest.Circulation research · 2026Article
- Cardiac Pacemaker Cells Harness Stochastic Resonance to Ensure Fail-Safe Operation at Low Rates Bordering on Sinus Arrest.bioRxiv : the preprint server for biology · 2026Article
- Beat-locked ATP microdomains in the sinoatrial node map a Ca2+-timed energetic hierarchy and regional pacemaker roles.The Journal of general physiology · 2026Article
- Emerging Regulatory Mechanisms in Sinoatrial Node Automaticity.Journal of cellular and molecular medicine · 2026Review
- L-Type CaCirculation research · 2026Article
- HCN4 gain-of-function mutation increases intrinsic heart rate and limits maladaptive remodeling under pressure overload.Frontiers in pharmacology · 2026Article
- Heart Rhythm Harmony Becomes Discordant as We Age.Heart, lung & circulation · 2025Review
- Deep Learning-Based Ion Channel Kinetics Analysis for Automated Patch Clamp Recording.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- HCN4 channels sense temperature and determine heart rate responses to heat.Nature communications · 2025Article
- Cardiac automaticity is modulated by IKACh in sinoatrial node during pregnancy.Cardiovascular research · 2024Article
- Activation of IPAmerican journal of physiology. Heart and circulatory physiology · 2024Article
- Cannabidiol potentiates hyperpolarization-activated cyclic nucleotide-gated (HCN4) channels.The Journal of general physiology · 2024Article
- Pacemaker Channels and the Chronotropic Response in Health and Disease.Circulation research · 2024Review
- Cardiac conduction diseases: understanding the molecular mechanisms to uncover targets for future treatments.Expert opinion on therapeutic targets · 2024Review
- Mitochondrial dysfunction is a key link involved in the pathogenesis of sick sinus syndrome: a review.Frontiers in cardiovascular medicine · 2024Review
- Compartmentalized cAMP signalling and control of cardiac rhythm.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- What makes the sinoatrial node tick? A question not for the faint of heart.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Genetics of sinoatrial node function and heart rate disorders.Disease models & mechanisms · 2023Review
- Cardiac RGS Proteins in Human Heart Failure and Atrial Fibrillation: Focus on RGS4.International journal of molecular sciences · 2023Review
- A novel conceptual model of heart rate autonomic modulation based on a small-world modular structure of the sinoatrial node.Frontiers in physiology · 2023Article
Corrections and comments
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Authors and funding
21 authors at 9 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is highly debated how cyclic adenosine monophosphate-dependent regulation (CDR) of the major pacemaker channel HCN4 in the sinoatrial node (SAN) is involved in heart rate regulation by the autonomic nervous system. We addressed this question using a knockin mouse line expressing cyclic adenosine monophosphate-insensitive HCN4 channels. This mouse line displayed a complex cardiac phenotype characterized by sinus dysrhythmia, severe sinus bradycardia, sinus pauses and chronotropic incompetence. Furthermore, the absence of CDR leads to inappropriately enhanced heart rate responses of the SAN to vagal nerve activity in vivo. The mechanism underlying these symptoms can be explained by the presence of nonfiring pacemaker cells. We provide evidence that a tonic and mutual interaction process (tonic entrainment) between firing and nonfiring cells slows down the overall rhythm of the SAN. Most importantly, we show that the proportion of firing cells can be increased by CDR of HCN4 to efficiently oppose enhanced responses to vagal activity. In conclusion, we provide evidence for a novel role of CDR of HCN4 for the central pacemaker process in the sinoatrial node.
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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.