Imperial College London
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ProfessorPeterKohl

Faculty of Medicine, National Heart & Lung Institute

Visiting Professor
 
 
 
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Contact

 

p.kohl Website

 
 
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Location

 

Heart Science CentreHarefield Hospital

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Summary

 

Publications

Citation

BibTex format

@article{Kong:2018:10.1073/pnas.1805979115,
author = {Kong, CHT and Rog-Zielinska, EA and Kohl, P and Orchard, CH and Cannell, MB},
doi = {10.1073/pnas.1805979115},
journal = {Proceedings of the National Academy of Sciences},
pages = {E7073--E7080},
title = {Solute movement in the t-tubule system of rabbit and mouse cardiomyocytes},
url = {http://dx.doi.org/10.1073/pnas.1805979115},
volume = {115},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Cardiac transverse (t-) tubules carry both electrical excitation and solutes toward the cell center but their ability to transport small molecules is unclear. While fluorescence recovery after photobleaching (FRAP) can provide an approach to measure local solute movement, extraction of diffusion coefficients is confounded by cell and illumination beam geometries. In this study, we use measured cellular geometry and detailed computer modeling to derive the apparent diffusion coefficient of a 1-kDa solute inside the t-tubular system of rabbit and mouse ventricular cardiomyocytes. This approach shows that diffusion within individual t-tubules is more rapid than previously reported. T-tubule tortuosity, varicosities, and the presence of longitudinal elements combine to substantially reduce the apparent rate of solute movement. In steady state, large (>4 kDa) solutes did not freely fill the t-tubule lumen of both species and <50% of the t-tubule volume was available to solutes >70 kDa. Detailed model fitting of FRAP data suggests that solute diffusion is additionally restricted at the t-tubular entrance and this effect was larger in mouse than in rabbit. The possible structural basis of this effect was investigated using electron microscopy and tomography. Near the cell surface, mouse t-tubules are more tortuous and filled with an electron-dense ground substance, previously identified as glycocalyx and a polyanionic mesh. Solute movement in the t-tubule network of rabbit and mouse appears to be explained by their different geometric properties, which impacts the use of these species for understanding t-tubule function and the consequences of changes associated with t-tubule disease.
AU  - Kong,CHT
AU  - Rog-Zielinska,EA
AU  - Kohl,P
AU  - Orchard,CH
AU  - Cannell,MB
DO  - 10.1073/pnas.1805979115
EP  - 7080
PY  - 2018///
SN  - 0027-8424
SP  - 7073
TI  - Solute movement in the t-tubule system of rabbit and mouse cardiomyocytes
T2  - Proceedings of the National Academy of Sciences
UR  - http://dx.doi.org/10.1073/pnas.1805979115
UR  - https://www.ncbi.nlm.nih.gov/pubmed/29991602
UR  - http://hdl.handle.net/10044/1/61500
VL  - 115
ER  -
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