ArticleScience translational medicine2017
Redundant and diverse intranodal pacemakers and conduction pathways protect the human sinoatrial node from failure.
Article in Science translational medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 99 citations in OpenAlex.
- Sinoatrial Node Impulses Emerge From Unique Synchronization Processing Solutions of Partially Stochastic Local Calcium Signals.JACC. Clinical electrophysiology · 2026Article
- The cardiac pacemakers: A paradigm of robustness in evolutionary biology.The Journal of physiology · 2026Review
- 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
- Inferior Sino-Atrial Node Exit Sites Are Associated With Electrical Remodeling.JACC. Clinical electrophysiology · 2026Article
- Emerging Regulatory Mechanisms in Sinoatrial Node Automaticity.Journal of cellular and molecular medicine · 2026Review
- Mechanisms of rectified gap junctional coupling enhancing pacemaking activity of biologically engineered pacemaker cells.NPJ systems biology and applications · 2026Article
- An efficient end-to-end computational framework for the generation of ECG calibrated volumetric models of human atrial electrophysiology.Medical image analysis · 2026Article
- Stress-induced pacemaker desynchronization in the sinoatrial node.Frontiers in cardiovascular medicine · 2026Article
- Selective sinoatrial suppression during post-ablation adenosine testing without atrioventricular block.European heart journal. Case reports · 2026Article
- Aging and sinus node dysfunction: mechanisms and future directions.Clinical science (London, England : 1979) · 2025Review
- Phasic effects of cardiac-synchronized vagus nerve stimulation on spatiotemporal behavior of the sinoatrial node in swine.Heart rhythm O2 · 2025Article
- Heart Rate Mystery Unveiled: Sex Differences in Human Sinoatrial Node Genes and Female Tachycardia.Circulation. Arrhythmia and electrophysiology · 2025Article
- Morphometric and histological changes in cardiac nodes after acute spontaneous myocardial infarction in humans and pigs.Veterinary world · 2024Article
- Pacemaker Channels and the Chronotropic Response in Health and Disease.Circulation research · 2024Review
- Cardiac Development at a Single-Cell Resolution.Advances in experimental medicine and biology · 2024Article
- Sinoatrial node heterogeneity and fibroblasts increase atrial driving capability in a two-dimensional human computational model.Frontiers in physiology · 2024Article
- Mechanistic insight into the functional role of human sinoatrial node conduction pathways and pacemaker compartments heterogeneity: A computer model analysis.PLoS computational biology · 2023Article
- Relevance ofInternational journal of molecular 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
9 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
Abstract
The human sinoatrial node (SAN) efficiently maintains heart rhythm even under adverse conditions. However, the specific mechanisms involved in the human SAN's ability to prevent rhythm failure, also referred to as its robustness, are unknown. Challenges exist because the three-dimensional (3D) intramural structure of the human SAN differs from well-studied animal models, and clinical electrode recordings are limited to only surface atrial activation. Hence, to innovate the translational study of human SAN structural and functional robustness, we integrated intramural optical mapping, 3D histology reconstruction, and molecular mapping of the ex vivo human heart. When challenged with adenosine or atrial pacing, redundant intranodal pacemakers within the human SAN maintained automaticity and delivered electrical impulses to the atria through sinoatrial conduction pathways (SACPs), thereby ensuring a fail-safe mechanism for robust maintenance of sinus rhythm. During adenosine perturbation, the primary central SAN pacemaker was suppressed, whereas previously inactive superior or inferior intranodal pacemakers took over automaticity maintenance. Sinus rhythm was also rescued by activation of another SACP when the preferential SACP was suppressed, suggesting two independent fail-safe mechanisms for automaticity and conduction. The fail-safe mechanism in response to adenosine challenge is orchestrated by heterogeneous differences in adenosine A1 receptors and downstream GIRK4 channel protein expressions across the SAN complex. Only failure of all pacemakers and/or SACPs resulted in SAN arrest or conduction block. Our results unmasked reserve mechanisms that protect the human SAN pacemaker and conduction complex from rhythm failure, which may contribute to treatment of SAN arrhythmias.
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