Analysis of ryanodine receptor clusters in rat and human cardiac myocyte

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dc.contributor.author Soeller, Christian en
dc.contributor.author Crossman, David en
dc.contributor.author Gilbert, Raymond en
dc.contributor.author Cannell, Mark en
dc.date.accessioned 2012-03-25T20:55:16Z en
dc.date.issued 2007 en
dc.identifier.citation PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 104(38):14958-14963 18 Sep 2007 en
dc.identifier.issn 1091-6490 en
dc.identifier.uri http://hdl.handle.net/2292/15219 en
dc.description.abstract Single rat ventricular myocytes and human ventricle tissue sections were labeled with antibodies against the ryanodine receptor (RyR) and -actinin to examine the 3D distribution of RyRs with confocal microscopy. Image contrast was maximized by refractive index matching and deconvolution. The RyR label formed discrete puncta representing clusters of RyRs or ‘‘couplons’’ around the edges of the myofilaments with a nearest-neighbor spacing of 0.66 0.06 m in rat and 0.78 0.07 m in human. Each bundle of myofibrils was served by approximately six couplons, which supplied a cross-sectional area of 0.6 m2 in rat and 0.8 m2 in human. Although the couplons were in reasonable registration with zlines, there were discontinuities in the longitudinal position of sarcomeres so that dislocations in the order of RyR clusters occurred. There was 53% longitudinal registration of RyR clusters, suggesting a nonrandom placement of couplons around the sarcomere. These data can explain the spherical propagation of Ca 2 waves and provide quantitative 3D data sets needed for accurate modeling of cardiac Ca 2 -induced Ca 2 release. By quantifying labeling intensity in rat ventricular myocytes, a lower limit of 78 RyRs per cluster (on average) was obtained. By modeling the couplon as a disk wrapping around a t-tubule and fitting cluster images, 95% of couplons contained between 120 and 260 RyRs (assuming that RyRs are tight packed with a spacing of 29 nm). Assuming similar labeling efficiency in human, from the fluorescence intensity alone we estimate that human ventricular myocytes contain 30% fewer RyRs per couplon than rat. en
dc.publisher The National Academy of Sciences of the USA en
dc.relation.ispartofseries Proceedings of the National Academy of Sciences of the United States of America en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/1091-6490/ en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.title Analysis of ryanodine receptor clusters in rat and human cardiac myocyte en
dc.type Journal Article en
dc.identifier.doi 10.1073/pnas.0703016104 en
pubs.issue 38 en
pubs.begin-page 14958 en
pubs.volume 104 en
dc.rights.holder Copyright: The National Academy of Sciences of the USA en
dc.identifier.pmid 17848521 en
pubs.end-page 14963 en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype Article en
pubs.elements-id 75835 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Medical Sciences en
pubs.org-id Physiology Division en
pubs.org-id Science en
pubs.org-id Science Research en
pubs.org-id Maurice Wilkins Centre (2010-2014) en
pubs.record-created-at-source-date 2010-09-01 en
pubs.dimensions-id 17848521 en


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