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Solute movement in the t-tubule system of rabbit and mouse cardiomyocytes

Research output: Contribution to journalArticle

  • Cherrie Kong
  • Eva Rog-Zielinska
  • Peter Kohl
  • Clive Orchard
  • Mark Cannell
Original languageEnglish
Pages (from-to)E7073-E7080
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number30
Early online date10 Jul 2018
DOIs
DateAccepted/In press - 15 Jun 2018
DateE-pub ahead of print - 10 Jul 2018
DatePublished (current) - 24 Jul 2018

Abstract

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.

    Research areas

  • Cardiac myocytes, Diffusion, FRAP, Structure, t-tubules

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via PNAS at http://www.pnas.org/content/early/2018/07/09/1805979115 . Please refer to any applicable terms of use of the publisher.

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