Changes in the organization of excitation-contraction coupling structures in failing human heart
dc.contributor.author | Crossman, DJ | |
dc.contributor.author | Ruygrok, PR | |
dc.contributor.author | Soeller, C | |
dc.contributor.author | Cannell, MB | |
dc.date.accessioned | 2019-03-21T09:01:26Z | |
dc.date.issued | 2011-03-14 | |
dc.description.abstract | Background: The cardiac myocyte t-tubular system ensures rapid, uniform cell activation and several experimental lines of evidence suggest changes in the t-tubular system and associated excitation-contraction coupling proteins may occur in heart failure. Methods and Results: The organization of t-tubules, L-type calcium channels (DHPRs), ryanodine receptors (RyRs) and contractile machinery were examined in fixed ventricular tissue samples from both normal and failing hearts (idiopathic (non-ischemic) dilated cardiomyopathy) using high resolution fluorescent imaging. Wheat germ agglutinin (WGA), Na-Ca exchanger, DHPR and caveolin-3 labels revealed a shift from a predominantly transverse orientation to oblique and axial directions in failing myocytes. In failure, dilation of peripheral t-tubules occurred and a change in the extent of protein glycosylation was evident. There was no change in the fractional area occupied by myofilaments (labeled with phalloidin) but there was a small reduction in the number of RyR clusters per unit area. The general relationship between DHPRs and RyR was not changed and RyR labeling overlapped with 51±3% of DHPR labeling in normal hearts. In longitudinal (but not transverse) sections there was an ~30% reduction in the degree of colocalization between DHPRs and RyRs as measured by Pearson's correlation coefficient in failing hearts. Conclusions: The results show that extensive remodelling of the t-tubular network and associated excitation-contraction coupling proteins occurs in failing human heart. These changes may contribute to abnormal calcium handling in heart failure. The general organization of the t-system and changes observed in failure samples have subtle differences to some animal models although the general direction of changes are generally similar. © 2011 Crossman et al. | en_GB |
dc.description.sponsorship | Health Research Council of New Zealand | en_GB |
dc.identifier.citation | Vol. 6, e17901 | en_GB |
dc.identifier.doi | 10.1371/journal.pone.0017901 | |
dc.identifier.grantnumber | 05/049 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/36584 | |
dc.language.iso | en | en_GB |
dc.publisher | Public Library of Science | en_GB |
dc.rights | © 2011 Crossman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | en_GB |
dc.title | Changes in the organization of excitation-contraction coupling structures in failing human heart | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2019-03-21T09:01:26Z | |
dc.description | This is the final version. Available from the publisher via the DOI in this record. | en_GB |
dc.identifier.journal | PLoS ONE | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
pubs.euro-pubmed-id | MED:21408028 | |
dcterms.dateAccepted | 2011-02-14 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2011-03-14 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2019-03-21T08:51:03Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2019-03-21T09:01:36Z | |
refterms.panel | B | en_GB |
refterms.dateFirstOnline | 2011-03-09 |
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Except where otherwise noted, this item's licence is described as © 2011 Crossman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.