DOI: 10.1161/01.res.0000089258.40661.0c. Coupling of Cardiac Electrical Activity Over Extended Distances by Fibroblasts of Cardiac Origin

Coupling of Cardiac Electrical Activity Over Extended Distances by Fibroblasts of Cardiac Origin

10.1161/01.res.0000089258.40661.0c

Crossref journal-article

Ovid Technologies (Wolters Kluwer Health)

Circulation Research (276)

Abstract

Roughly half of the cells of the heart consist of nonmyocardial cells, with fibroblasts representing the predominant cell type. It is well established that individual cardiomyocytes and fibroblasts in culture establish gap junctional communication at the single cell level (short-range interaction). However, it is not known whether such coupling permits activation of cardiac tissue over extended distances (long-range interaction). Long-range interactions may be responsible for electrical synchronization of donor and recipient tissue after heart transplantation and may play a role in arrhythmogenesis. This question was investigated using a novel heterocellular culture model with strands of cardiomyocytes interrupted by cardiac fibroblasts over defined distances. With use of optical recording techniques, it could be shown that impulse propagation along fibroblast inserts was successful over distances up to 300 μm and was characterized by length-dependent local propagation delays ranging from 11 to 68 ms (apparent local “conduction velocities” 4.6±1.8 mm/s, n=23). Involvement of mechanical stretch in this phenomenon was excluded by showing that inserts consisting of communication-deficient HeLa cells were incapable of supporting propagation. In contrast, HeLa cells expressing connexin43 permitted impulse conduction over distances as long as 600 μm. Immunocytochemistry showed that fibroblasts and cardiomyocytes expressed connexin43 and connexin45, whereas connexin40 was absent. These results illustrate that fibroblasts of cardiac origin are capable of synchronizing electrical activity of multicellular cardiac tissue over extended distances through electrotonic interactions. This synchronization is accompanied by extremely large local conduction delays, which might contribute to the generation of arrhythmias in fibrotic hearts.

Bibliography

Gaudesius, G., Miragoli, M., Thomas, S. P., & Rohr, S. (2003). Coupling of Cardiac Electrical Activity Over Extended Distances by Fibroblasts of Cardiac Origin. Circulation Research, 93(5), 421â428.

Authors 4

Giedrius Gaudesius (first)
Michele Miragoli (additional)
Stuart P. Thomas (additional)
Stephan Rohr (additional)

References 28 Referenced 431

Nag AC. Study of non-muscle cells of the adult mammalian heart: a fine structural analysis and distribution. Cytobios. 1980; 28: 41–61. / Cytobios (1980)
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10.1126/science.2449730
De Roos ADG, Willems PHGM, Van Zoelen EJJ, Theuvenet APR. Synchronized Ca2+ signaling by intercellular propagation of Ca2+ action potentials in NRK fibroblasts. Am J Physiol. 1997; 42: C1900–C1907. / Am J Physiol (1997)
10.1016/0022-2828(92)91041-3
Weber K. Cardiac interstitium. In: Poole-Wilson P Colucci WBM Chatterjee K Coats A eds. Heart Failure. New York NY: Churchill Livingstone; 1997: 13–31.
10.1152/physrev.1999.79.1.215
Willems IEMG, Havenith MG, De Mey JGR, Daemen MJAP. The a-smooth muscle actin-positive cells in healing human myocardial scars. Am J Pathol. 1994; 145: 868–875. / Am J Pathol (1994)
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10.1152/ajpcell.1999.277.1.C1
10.1002/(SICI)1096-9896(199801)184:1<37::AID-PATH966>3.0.CO;2-D
Spanakis SG, Petridou S, Masur SK. Functional gap junctions in corneal fibroblasts and myofibroblasts. Invest Ophthalmol Vis Sci. 1998; 39: 1320–1328. / Invest Ophthalmol Vis Sci (1998)
10.1161/res.83.8.781

Dates

Type	When
Created	22 years ago (Aug. 4, 2003, 8:30 p.m.)
Deposited	1 year, 3 months ago (May 12, 2024, 2:30 p.m.)
Indexed	3 weeks, 4 days ago (Aug. 2, 2025, 12:08 a.m.)
Issued	21 years, 11 months ago (Sept. 5, 2003)
Published	21 years, 11 months ago (Sept. 5, 2003)
Published Print	21 years, 11 months ago (Sept. 5, 2003)

Funders 0

None

BibTeX

@article{Gaudesius_2003, title={Coupling of Cardiac Electrical Activity Over Extended Distances by Fibroblasts of Cardiac Origin}, volume={93}, ISSN={1524-4571}, url={http://dx.doi.org/10.1161/01.res.0000089258.40661.0c}, DOI={10.1161/01.res.0000089258.40661.0c}, number={5}, journal={Circulation Research}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Gaudesius, Giedrius and Miragoli, Michele and Thomas, Stuart P. and Rohr, Stephan}, year={2003}, month=sep, pages={421–428} }

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