Jayasinghe, I orcid.org/0000-0003-2461-478X, Clowsley, AH, de Langen, O et al. (3 more authors) (2018) Shining New Light on the Structural Determinants of Cardiac Couplon Function: Insights From Ten Years of Nanoscale Microscopy. Frontiers in Physiology, 9. ARTN 1472. ISSN 1664-042X
Abstract
Remodelling of the membranes and protein clustering patterns during the pathogenesis of cardiomyopathies has renewed the interest in spatial visualisation of these structures in cardiomyocytes. Coincidental emergence of single molecule (super-resolution) imaging and tomographic electron microscopy tools in the last decade have led to a number of new observations on the structural features of the couplons, the primary sites of excitation-contraction coupling in the heart. In particular, super-resolution and tomographic electron micrographs have revised and refined the classical views of the nanoscale geometries of couplons, t-tubules and the organisation of the principal calcium handling proteins in both healthy and failing hearts. These methods have also allowed the visualisation of some features which were too small to be detected with conventional microscopy tools. With new analytical capabilities such as single-protein mapping, in situ protein quantification, correlative and live cell imaging we are now observing an unprecedented interest in adapting these research tools across the cardiac biophysical research discipline. In this article, we review the depth of the new insights that have been enabled by these tools toward understanding the structure and function of the cardiac couplon. We outline the major challenges that remain in these experiments and emerging avenues of research which will be enabled by these technologies.
Metadata
Item Type: | Article |
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Copyright, Publisher and Additional Information: | Copyright © 2018 Jayasinghe, Clowsley, de Langen, Sali, Crossman and Soeller. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
Keywords: | cardiac muscle; couplons; super-resolution; localization microscopy; ryanodine receptors |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Funding Information: | Funder Grant number Wellcome Trust 207684/Z/17/Z |
Depositing User: | Symplectic Publications |
Date Deposited: | 05 Nov 2018 13:43 |
Last Modified: | 05 Nov 2018 13:43 |
Status: | Published |
Publisher: | Frontiers Media |
Identification Number: | 10.3389/fphys.2018.01472 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:138172 |