Real-Time In Vivo Imaging of Mouse Left Ventricle Reveals Fluctuating Movements of the Intercalated Discs

Nanomaterials

Takako Terui¹  Tomohiro Nakanishi²  Fuyu Kobirumaki-Shimozawa²  Kotaro Oyama²  Norio Fukuda²  Shin’ichi Ishiwata³  Jia Li⁴  WilliamE. Louch⁴  Togo Shimozawa⁵ 

[1] Department of Anesthesiology, The Jikei University School of Medicine, Tokyo 105-8461, Japan;Department of Cell Physiology, The Jikei University School of Medicine, Tokyo 105-8461, Japan;Department of Physics, Faculty of Science and Engineering, Waseda University, Tokyo 169-8555, Japan;Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, 0450 Oslo, Norway;Technical Division, School of Science, The University of Tokyo, Tokyo 113-0033, Japan;

关键词: myocardium;    gap junction;    action potential;    heart;   

DOI  :  10.3390/nano10030532

来源: DOAJ

【 摘 要 】

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_v1.5 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 α-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_v1.5 by promoting ephaptic conduction in coordination with electronic conduction, and, thereby, efficiently transmitting excitation-contraction coupling between cardiomyocytes.

【 授权许可】

Unknown