ArticleNature communications2014
Exercise training reduces resting heart rate via downregulation of the funny channel HCN4.
Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 3 of them syntheses that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
108 citing papers in PubMed, 3 syntheses or guidelines pooled it, 266 citations in OpenAlex.
- The Dual Nature of Sinoatrial Node Remodelling in Athletes: A Systematic Review of Electrophysiological Adaptations and the Pathological Tipping Point.International journal of molecular sciences · 2025Pooled it
- The effects of exercise training on hypertensive older adults: an umbrella meta-analysis.Hypertension research : official journal of the Japanese Society of Hypertension · 2021Pooled it
- Expert consensus document: Defining the major health modifiers causing atrial fibrillation: a roadmap to underpin personalized prevention and treatment.Nature reviews. Cardiology · 2016Guideline
- Physiological and Cardiac Effects of Weight Loss in Adolescents With Atypical Anorexia Nervosa Versus Those Undergoing Bariatric Surgery: A Retrospective Comparative Study.Journal of paediatrics and child health · 2026Article
- Cardiorespiratory and autonomic trajectories in cadets training for general versus strength endurance, with differential ventilatory economization: a 4-month observational study.European journal of applied physiology · 2026Article
- Aerobic Endurance Training Modulates Cardiac Renin-Angiotensin System Peptides and Matrix Metalloproteinase Activity During Chronic Stress.Journal of cellular and molecular medicine · 2026Article
- Exercise-Induced Complete Heart Block and Sinoatrial Exit Block in Baseline Bifascicular Block.The American journal of case reports · 2026Article
- Effects of Exercise Training on Left Ventricular Hypertrophy and Cardiac Regulation in Elite Athletes: Insight from a Composite Index Proxy of Autonomic Control.Journal of cardiovascular development and disease · 2026Article
- A new Fight-or-Flight Pacemaker Mechanism via Ryanodine Receptor abundance and superclustering.PLoS computational biology · 2026Article
- Bradycardia in Athletes: Prevalence, Mechanisms, and Risks.Circulation · 2026Article
- AMPK-mediated HCN4 channel phosphorylation contributes to age-related intrinsic bradycardia.The Journal of general physiology · 2026Article
- A custom analysis of R-R interval properties reveals alterations in the brain-heart axis in experimental animals with metabolic syndrome.Heart rhythm O2 · 2026Article
- Yo-Yo IR1-derived aerobic endurance machine-learning prediction in youth male soccer players using demographics information and resting heart rate variability parameters.Frontiers in physiology · 2026Article
- Cardiac Adaptations in Endurance Athletes: A Bibliometric Analysis of Exercise‑Induced Physiologic Remodeling.Orthopedic reviews · 2026Article
- Improvements in body composition, functional capacity, and cardiovascular fitness: results of a workplace wellness program in the United Arab Emirates.Frontiers in sports and active living · 2026Article
- Impact of Anatomical Placement on the Accuracy of Wearable Heart Rate Monitors During Rest and Various Exercise Intensities.Sensors (Basel, Switzerland) · 2025Article
- Article
- Pharmacological Preconditioning with Diazoxide Upregulates HCN4 Channels in the Sinoatrial Node of Adult Rat Cardiomyocytes.International journal of molecular sciences · 2025Article
- Aging and sinus node dysfunction: mechanisms and future directions.Clinical science (London, England : 1979) · 2025Review
- Mapping HRV in sports science: from monitoring to machine learning.Frontiers in sports and active living · 2025Review
48 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
Endurance athletes exhibit sinus bradycardia, that is a slow resting heart rate, associated with a higher incidence of sinus node (pacemaker) disease and electronic pacemaker implantation. Here we show that training-induced bradycardia is not a consequence of changes in the activity of the autonomic nervous system but is caused by intrinsic electrophysiological changes in the sinus node. We demonstrate that training-induced bradycardia persists after blockade of the autonomous nervous system in vivo in mice and in vitro in the denervated sinus node. We also show that a widespread remodelling of pacemaker ion channels, notably a downregulation of HCN4 and the corresponding ionic current, If. Block of If abolishes the difference in heart rate between trained and sedentary animals in vivo and in vitro. We further observe training-induced downregulation of Tbx3 and upregulation of NRSF and miR-1 (transcriptional regulators) that explains the downregulation of HCN4. Our findings provide a molecular explanation for the potentially pathological heart rate adaptation to exercise training.
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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.