Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 113, Issue 51, Pages 14852-14857Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1611184114
Keywords
cardiac; electrophysiology; fibroblast; heterocellular coupling; genetically-encoded voltage indicator
Categories
Funding
- NIH [P41-GM103431]
- Canadian Institutes of Health Research [MOP-142424]
- Natural Sciences and Engineering Research Council [RGPIN-2016-04879]
- Nova Scotia Health Research Foundation [MED-EST-2014-9582]
- RIKEN Intramural Grant
- European Research Council Advanced Grant CardioNECT
- Magdi Yacoub Institute
- British Heart Foundation [FS/12/17/29532, FS/15/3/31047] Funding Source: researchfish
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available