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Macrophages Facilitate Electrical Conduction in the Heart
Open accessAbstract
Organ-specific functions of tissue-resident macrophages in the steady-state heart are unknown. Here, we show that cardiac macrophages facilitate electrical conduction through the distal atrioventricular node, where conducting cells densely intersperse with elongated macrophages expressing connexin 43. When coupled to spontaneously beating cardiomyocytes via connexin-43-containing gap junctions, cardiac macrophages have a negative resting membrane potential and depolarize in synchrony with cardiomyocytes. Conversely, macrophages render the resting membrane potential of cardiomyocytes more positive and, according to computational modeling, accelerate their repolarization. Photostimulation of channelrhodopsin-2-expressing macrophages improves atrioventricular conduction, whereas conditional deletion of connexin 43 in macrophages and congenital lack of macrophages delay atrioventricular conduction. In the Cd11b DTR mouse, macrophage ablation induces progressive atrioventricular block. These observations implicate macrophages in normal and aberrant cardiac conduction.
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“Under physiological conditions, this crosstalk is vital for maintaining electrical stability and metabolic homeostasis through the efferocytosis of damaged mitochondria [11,12].”
From Cardiac Macrophages Exhibit Dynamic Heterogeneity and Functional Specialization During Experimental Autoimmune Myocarditis. (2026) · cites this paper as [11]
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“Additionally, macrophages have been identified as key factors influencing cardiac remodelling and fibrosis [2,3].”
From Elucidating cardiac fibroblasts heterogeneity and activation during experimental autoimmune myocarditis using spatial transcriptomics. (2025) · cites this paper as [2]
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Metadata
- Authors
- Hulsmans, M., Clauss, S., Xiao, L., Aguirre, A. D., King, K. R., Hanley, A., Hucker, W. J., Wülfers, E. M., Seemann, G., Courties, G., Iwamoto, Y., Sun, Y., Savol, A. J., Sager, H. B., Lavine, K. J., Fishbein, G. A., Capen, D. E., Da Silva, N., Miquerol, L., Wakimoto, H., Seidman, C. E., Seidman, J. G., Sadreyev, R. I., Naxerova, K., Mitchell, R. N., Brown, D., Libby, P., Weissleder, R., Swirski, F. K., Kohl, P., Vinegoni, C., Milan, D. J., Ellinor, P. T., & Nahrendorf, M.
- Affiliations
- Harvard University (US)
- University of Freiburg (DE)
- Washington University in St. Louis (US)
- Brigham and Women's Hospital (US)
- Centre National de la Recherche Scientifique (FR)
- Broad Institute (US)
- Corresponding author
- Nahrendorf, Matthias
- ORCID
- Hulsmans, Maarten
- Clauss, Sebastian
- Xiao, Ling
- Aguirre, Aaron D.
- King, Kevin R.
- Hanley, Alan
- Hucker, William J.
- Wülfers, Eike M.
- Seemann, Gunnar
- Courties, Gabriel
- Iwamoto, Yoshiko
- Sager, Hendrik B.
- Lavine, Kory J.
- Fishbein, Gregory A.
- Capen, Diane E.
- Miquerol, Lucile
- Wakimoto, Hiroko
- Seidman, Christine E.
- Seidman, Jonathan G.
- Sadreyev, Ruslan I.
- Naxerova, Kamila
- Mitchell, Richard N.
- Brown, Dennis
- Libby, Peter
- Weissleder, Ralph
- Kohl, Peter
- Vinegoni, Claudio
- Milan, David J.
- Ellinor, Patrick T.
- Nahrendorf, Matthias
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2017-04
- Volume
- 169
- Issue
- 3
- Pages
- 510-522.e20
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5474950
- OpenAlex
- W2605696370
- Cited by
- 1,011
- References
- 53
- Citations by year
- 2026: 99 · 2025: 110 · 2024: 129 · 2023: 112 · 2022: 108 · 2021: 135 · 2020: 112 · 2019: 92 · 2018: 85 · 2017: 26
- FWCI
- 66.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Arrow@dit (Dublin Institute of Technology) (submittedVersion)
- HAL (submittedVersion)
- ARAN (University of Galway Research Repository) (Ollscoil na Gaillimhe – University of Galway) (submittedVersion, cc-by-nc-nd)
- eScholarship (California Digital Library) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion, cc-by-nc-nd)
- Funders
- NIH (NS084863, HL128264, HL114477, HL117829, HL092577, HD069623, HL105780, HL096576)
- Inflammatory Bowel Disease Grant (DK43351)
- Boston Area Diabetes and Endocrinology Research Center (BADERC) Award (DK57521)
- Fonds voor Wetenschappelijk Onderzoek-Vlaanderen
- Marie Curie International Outgoing Fellowship
- 7th European Community Framework Program (PIOF-GA-2012-328352)
- German Center for Cardiovascular Research (DZHK
- American Heart Association (14FTF20380185, 13EIA14220013)
- Deutsche Forschungsgemeinschaft (SA1668/2-1)
- European Research Council Advanced Grant CardioNect
- Baden Wurttemberg Sonderlinie Medizin
- Established Investigator Award
- Fondation Leducq (14CVD01)
- MGH Research Scholar Program
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- cardiac macrophages, atrioventricular node, cardiac conduction, connexin 43, gap junctions, atrioventricular block, channelrhodopsin-2, macrophage depletion, resting membrane potential, repolarization
- MeSH terms
- Animals, Female, Heart Atria, Heart Conduction System, Humans, Macrophages, Male, Mice, Inbred C57BL, Middle Aged, Connexin 43, Myocytes, Cardiac, Mice
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