ArticleThe Journal of physiology2007
The relevance of non-excitable cells for cardiac pacemaker function.
Article in The Journal of physiology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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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
38 citing papers in PubMed, 76 citations in OpenAlex.
- Heart Rhythm Harmony Becomes Discordant as We Age.Heart, lung & circulation · 2025Review
- Sinoatrial node heterogeneity and fibroblasts increase atrial driving capability in a two-dimensional human computational model.Frontiers in physiology · 2024Article
- Heart rhythmFrontiers in cardiovascular medicine · 2024Article
- The sinoatrial node extracellular matrix promotes pacemaker phenotype and protects automaticity in engineered heart tissues from cyclic strain.Cell reports · 2023Article
- The role of P21-activated kinase (Pak1) in sinus node function.Journal of molecular and cellular cardiology · 2023Article
- Sinus node dysfunction: current understanding and future directions.American journal of physiology. Heart and circulatory physiology · 2023Review
- Hippo-Yap Signaling Maintains Sinoatrial Node Homeostasis.Circulation · 2022Article
- Coupling and heterogeneity modulate pacemaking capability in healthy and diseased two-dimensional sinoatrial node tissue models.PLoS computational biology · 2022Article
- The Heart's Pacemaker Mimics Brain Cytoarchitecture and Function: Novel Interstitial Cells Expose Complexity of the SAN.JACC. Clinical electrophysiology · 2022Article
- Transthyretin deposition alters cardiomyocyte sarcomeric architecture, calcium transients, and contractile force.Physiological reports · 2022Article
- Assembly of the Cardiac Pacemaking Complex: Electrogenic Principles of Sinoatrial Node Morphogenesis.Journal of cardiovascular development and disease · 2021Review
- Review
- Optically activated, customizable, excitable cells.PloS one · 2020Article
- Human Cardiac Fibroblast Number and Activation State Modulate Electromechanical Function of hiPSC-Cardiomyocytes in Engineered Myocardium.Stem cells international · 2020Article
- In vitro study of the effects of reprogramming neonatal rat fibroblasts transfected with TBX18 on spontaneous beating in neonatal rat cardiomyocytes.Molecular medicine reports · 2018Article
- Intercellular Connectivity and Multicellular Bioelectric Oscillations in Nonexcitable Cells: A Biophysical Model.ACS omega · 2018Article
- Dynamic Cellular Integration Drives Functional Assembly of the Heart's Pacemaker Complex.Cell reports · 2018Article
- Versatile Flexible Graphene Multielectrode Arrays.Biosensors · 2016Article
- Current concepts of anatomy and electrophysiology of the sinus node.Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing · 2016Review
- Electrical and mechanical stimulation of cardiac cells and tissue constructs.Advanced drug delivery reviews · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
Age-dependent changes in the architecture of the sinus node comprise an increasing ratio between fibroblasts and cardiomyocytes. This change is discussed as a potential mechanism for sinus node disease. The goal of this study was to determine the mechanism through which non-excitable cells influence the spontaneous activity of multicellular cardiomyocyte preparations. Cardiomyocyte monolayers (HL-1 cells) or embryonic stem cell-derived cardiomyocytes were used as two- and three-dimensional cardiac pacemaker models. Spontaneous activity and conduction velocity (theta) were monitored by field potential measurements with microelectrode arrays (MEAs). The influence of fibroblasts (WT-fibs) was determined in heterocellular cultures of different cardiomyocyte and fibroblast ratios. The relevance of heterocellular gap junctional coupling was evaluated by the use of fibroblasts deficient for the expression of Cx43 (Cx43(-/-)-fibs). The beating frequency and of heterocellular cultures depended negatively on the fibroblast concentration. Interspersion of fibroblasts in cardiomyocyte monolayers increased the coefficient of the interbeat interval variability. Whereas Cx43(-/-)-fibs decreased theta significantly less than WT-fibs, their effect on the beating frequency and the beat-to-beat variability seemed largely independent of their ability to establish intercellular coupling. These results suggest that electrically integrated, non-excitable cells modulate the excitability of cardiac pacemaker preparations by two distinct mechanisms, one dependent and the other independent of the heterocellular coupling established. Whereas heterocellular coupling enables the fibroblast to depolarize the cardiomyocytes or to act as a current sink, the mere physical separation of the cardiomyocytes by fibroblasts induces bradycardia through a reduction in frequency entrainment.
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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.