Real-Time In Vivo Imaging of Mouse Left Ventricle Reveals Fluctuating Movements of the Intercalated Discs
Myocardial contraction is initiated by action potential propagation through the conduction system of the heart. It has been thought that connexin 43 in the gap junctions (GJ) within the intercalated disc (ID) provides direct electric connectivity between cardiomyocytes (electronic conduction). Howev...
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MDPI AG
2020-03-01
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| Series: | Nanomaterials |
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| Online Access: | https://www.mdpi.com/2079-4991/10/3/532 |
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| author | Fuyu Kobirumaki-Shimozawa Tomohiro Nakanishi Togo Shimozawa Takako Terui Kotaro Oyama Jia Li William E. Louch Shin’ichi Ishiwata Norio Fukuda |
| author_facet | Fuyu Kobirumaki-Shimozawa Tomohiro Nakanishi Togo Shimozawa Takako Terui Kotaro Oyama Jia Li William E. Louch Shin’ichi Ishiwata Norio Fukuda |
| author_sort | Fuyu Kobirumaki-Shimozawa |
| collection | DOAJ |
| description | Myocardial contraction is initiated by action potential propagation through the conduction system of the heart. It has been thought that connexin 43 in the gap junctions (GJ) within the intercalated disc (ID) provides direct electric connectivity between cardiomyocytes (electronic conduction). However, recent studies challenge this view by providing evidence that the mechanosensitive cardiac sodium channels Na<sub>v</sub>1.5 localized in perinexii at the GJ edge play an important role in spreading action potentials between neighboring cells (ephaptic conduction). In the present study, we performed real-time confocal imaging of the CellMask-stained ID in the living mouse heart in vivo. We found that the ID structure was not rigid. Instead, we observed marked flexing of the ID during propagation of contraction from cell to cell. The variation in ID length was between ~30 and ~42 μm (i.e., magnitude of change, ~30%). In contrast, tracking of <i>α</i>-actinin-AcGFP revealed a comparatively small change in the lateral dimension of the transitional junction near the ID (i.e., magnitude of change, ~20%). The present findings suggest that, when the heart is at work, mechanostress across the perinexii may activate Na<sub>v</sub>1.5 by promoting ephaptic conduction in coordination with electronic conduction, and, thereby, efficiently transmitting excitation-contraction coupling between cardiomyocytes. |
| first_indexed | 2024-04-14T07:42:30Z |
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| institution | Directory Open Access Journal |
| issn | 2079-4991 |
| language | English |
| last_indexed | 2024-04-14T07:42:30Z |
| publishDate | 2020-03-01 |
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| series | Nanomaterials |
| spelling | doaj.art-b9179033fbdc427d92c3caf549bc28082022-12-22T02:05:27ZengMDPI AGNanomaterials2079-49912020-03-0110353210.3390/nano10030532nano10030532Real-Time In Vivo Imaging of Mouse Left Ventricle Reveals Fluctuating Movements of the Intercalated DiscsFuyu Kobirumaki-Shimozawa0Tomohiro Nakanishi1Togo Shimozawa2Takako Terui3Kotaro Oyama4Jia Li5William E. Louch6Shin’ichi Ishiwata7Norio Fukuda8Department of Cell Physiology, The Jikei University School of Medicine, Tokyo 105-8461, JapanDepartment of Cell Physiology, The Jikei University School of Medicine, Tokyo 105-8461, JapanTechnical Division, School of Science, The University of Tokyo, Tokyo 113-0033, JapanDepartment of Anesthesiology, The Jikei University School of Medicine, Tokyo 105-8461, JapanDepartment of Cell Physiology, The Jikei University School of Medicine, Tokyo 105-8461, JapanInstitute for Experimental Medical Research, Oslo University Hospital and University of Oslo, 0450 Oslo, NorwayInstitute for Experimental Medical Research, Oslo University Hospital and University of Oslo, 0450 Oslo, NorwayDepartment of Physics, Faculty of Science and Engineering, Waseda University, Tokyo 169-8555, JapanDepartment of Cell Physiology, The Jikei University School of Medicine, Tokyo 105-8461, JapanMyocardial contraction is initiated by action potential propagation through the conduction system of the heart. It has been thought that connexin 43 in the gap junctions (GJ) within the intercalated disc (ID) provides direct electric connectivity between cardiomyocytes (electronic conduction). However, recent studies challenge this view by providing evidence that the mechanosensitive cardiac sodium channels Na<sub>v</sub>1.5 localized in perinexii at the GJ edge play an important role in spreading action potentials between neighboring cells (ephaptic conduction). In the present study, we performed real-time confocal imaging of the CellMask-stained ID in the living mouse heart in vivo. We found that the ID structure was not rigid. Instead, we observed marked flexing of the ID during propagation of contraction from cell to cell. The variation in ID length was between ~30 and ~42 μm (i.e., magnitude of change, ~30%). In contrast, tracking of <i>α</i>-actinin-AcGFP revealed a comparatively small change in the lateral dimension of the transitional junction near the ID (i.e., magnitude of change, ~20%). The present findings suggest that, when the heart is at work, mechanostress across the perinexii may activate Na<sub>v</sub>1.5 by promoting ephaptic conduction in coordination with electronic conduction, and, thereby, efficiently transmitting excitation-contraction coupling between cardiomyocytes.https://www.mdpi.com/2079-4991/10/3/532myocardiumgap junctionaction potentialheart |
| spellingShingle | Fuyu Kobirumaki-Shimozawa Tomohiro Nakanishi Togo Shimozawa Takako Terui Kotaro Oyama Jia Li William E. Louch Shin’ichi Ishiwata Norio Fukuda Real-Time In Vivo Imaging of Mouse Left Ventricle Reveals Fluctuating Movements of the Intercalated Discs Nanomaterials myocardium gap junction action potential heart |
| title | Real-Time In Vivo Imaging of Mouse Left Ventricle Reveals Fluctuating Movements of the Intercalated Discs |
| title_full | Real-Time In Vivo Imaging of Mouse Left Ventricle Reveals Fluctuating Movements of the Intercalated Discs |
| title_fullStr | Real-Time In Vivo Imaging of Mouse Left Ventricle Reveals Fluctuating Movements of the Intercalated Discs |
| title_full_unstemmed | Real-Time In Vivo Imaging of Mouse Left Ventricle Reveals Fluctuating Movements of the Intercalated Discs |
| title_short | Real-Time In Vivo Imaging of Mouse Left Ventricle Reveals Fluctuating Movements of the Intercalated Discs |
| title_sort | real time in vivo imaging of mouse left ventricle reveals fluctuating movements of the intercalated discs |
| topic | myocardium gap junction action potential heart |
| url | https://www.mdpi.com/2079-4991/10/3/532 |
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