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dc.contributor.authorCrossman, DJ
dc.contributor.authorRuygrok, PR
dc.contributor.authorSoeller, C
dc.contributor.authorCannell, MB
dc.date.accessioned2019-03-21T09:01:26Z
dc.date.issued2011-03-14
dc.description.abstractBackground: 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.sponsorshipHealth Research Council of New Zealanden_GB
dc.identifier.citationVol. 6, e17901en_GB
dc.identifier.doi10.1371/journal.pone.0017901
dc.identifier.grantnumber05/049en_GB
dc.identifier.urihttp://hdl.handle.net/10871/36584
dc.language.isoenen_GB
dc.publisherPublic Library of Scienceen_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.titleChanges in the organization of excitation-contraction coupling structures in failing human hearten_GB
dc.typeArticleen_GB
dc.date.available2019-03-21T09:01:26Z
dc.descriptionThis is the final version. Available from the publisher via the DOI in this record.en_GB
dc.identifier.journalPLoS ONEen_GB
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_GB
pubs.euro-pubmed-idMED:21408028
dcterms.dateAccepted2011-02-14
rioxxterms.versionVoRen_GB
rioxxterms.licenseref.startdate2011-03-14
rioxxterms.typeJournal Article/Reviewen_GB
refterms.dateFCD2019-03-21T08:51:03Z
refterms.versionFCDVoR
refterms.dateFOA2019-03-21T09:01:36Z
refterms.panelBen_GB
refterms.dateFirstOnline2011-03-09


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© 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.
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.