Evidence map›Paper›PMID 27930302›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Electrotonic coupling of excitable and nonexcitable cells in the heart revealed by optogenetics.

T Alexander Quinn, Patrizia Camelliti, Eva A Rog-Zielinska, Urszula Siedlecka, Tommaso Poggioli, Eileen T O'Toole, Thomas Knöpfel, Peter Kohl

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers.

0numbers the graph read from it
0cells of the map it votes in
135citing papers in PubMed
12.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

135 citing papers in PubMed, 212 citations in OpenAlex.

  1. Review
  2. Article
  3. Interstitial cells and arrhythmia.American journal of physiology. Cell physiology · 2026
    Review
  4. Mechano-electrical feedback in transgenic rabbit models of long QT syndrome Type 2 and short QT syndrome Type 1.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026
    Article
  5. Review
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  7. Article
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  9. Article
  10. Atrial Fibroblasts-Derived Extracellular Vesicles Exacerbate Atrial Arrhythmogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  11. Review
  12. Article
  13. Article
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  15. Article
  16. Review
  17. Article
  18. Mitochondrial dysfunction as a central hub linking NaFrontiers in cardiovascular medicine · 2025
    Review
  19. Review
  20. Review

75 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 4 countries.

T Alexander QuinnDepartment of Physiology and Biophysics, Dalhousie University, Halifax, NS B3H 4R2, Canada; alex.quinn@dal.ca peter.kohl@universitaets-herzzentrum.de.
Patrizia CamellitiSchool of Biosciences and Medicine, University of Surrey, Guildford GU2 7XH, United Kingdom.
Eva A Rog-ZielinskaNational Heart and Lung Institute, Imperial College London, Harefield UB9 6JH, United Kingdom.
Urszula SiedleckaNational Heart and Lung Institute, Imperial College London, Harefield UB9 6JH, United Kingdom.
Tommaso PoggioliNational Heart and Lung Institute, Imperial College London, Harefield UB9 6JH, United Kingdom.
Eileen T O'TooleDepartment of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309.
Thomas KnöpfelDepartment of Medicine, Imperial College London, London W12 0NN, United Kingdom.
Peter KohlNational Heart and Lung Institute, Imperial College London, Harefield UB9 6JH, United Kingdom; alex.quinn@dal.ca peter.kohl@universitaets-herzzentrum.de.
Imperial College London · GBDalhousie University · CAUniversity of Colorado Boulder · USUniversity of Freiburg · DEUniversity of Surrey · GB

Funding

A MULTI-SCALE APPROACH TO CELL STRUCTURE & FUNCTIONP41GM103431 · NIGMS · UNIVERSITY OF COLORADO · PI HOENGER, ANDREAS · 2012 to 2014
$3.1M
British Heart Foundation FS/12/17/29532British Heart Foundation FS/15/3/31047CIHR MOP-142424NIGMS NIH HHS P41 GM103431
6 · The paper itself

Abstract

Electrophysiological studies of excitable organs usually focus on action potential (AP)-generating cells, whereas nonexcitable cells are generally considered as barriers to electrical conduction. Whether nonexcitable cells may modulate excitable cell function or even contribute to AP conduction via direct electrotonic coupling to AP-generating cells is unresolved in the heart: such coupling is present in vitro, but conclusive evidence in situ is lacking. We used genetically encoded voltage-sensitive fluorescent protein 2.3 (VSFP2.3) to monitor transmembrane potential in either myocytes or nonmyocytes of murine hearts. We confirm that VSFP2.3 allows measurement of cell type-specific electrical activity. We show that VSFP2.3, expressed solely in nonmyocytes, can report cardiomyocyte AP-like signals at the border of healed cryoinjuries. Using EM-based tomographic reconstruction, we further discovered tunneling nanotube connections between myocytes and nonmyocytes in cardiac scar border tissue. Our results provide direct electrophysiological evidence of heterocellular electrotonic coupling in native myocardium and identify tunneling nanotubes as a possible substrate for electrical cell coupling that may be in addition to previously discovered connexins at sites of myocyte-nonmyocyte contact in the heart. These findings call for reevaluation of cardiac nonmyocyte roles in electrical connectivity of the heterocellular heart.

Indexed as

OptogeneticsAction PotentialsAnimalsBacterial ProteinsCell CommunicationCell CountCell MembraneConnexinsElectric ConductivityFemaleFibroblastsGap JunctionsHeartHeart Conduction SystemLuminescent ProteinsMaleBacterial ProteinsConnexinsLuminescent Proteinsyellow fluorescent protein, Bacteriacardiacelectrophysiologyfibroblastgenetically-encoded voltage indicatorheterocellular coupling

Identifiers

PMID27930302
PMCPMC5187735
OpenAlexW2560738143

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.