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dc.contributor.authorSim, Jingweien
dc.contributor.authorFraser, Jamesen
dc.date.accessioned2014-10-20T13:42:25Z
dc.date.available2014-10-20T13:42:25Z
dc.date.issued2014-12-15en
dc.identifier.citationThe Journal of Physiology 592: 5477–5492. doi: 10.1113/jphysiol.2014.281170en
dc.identifier.issn0022-3751
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/246220
dc.description.abstractThe transverse tubular (t-) system of skeletal muscle couples sarcolemmal electrical excitation with contraction deep within the fibre. Exercise, pathology, and the composition of the extracellular fluid (ECF) can alter t-system volume (t-volume). T-volume changes likely contribute to fatigue, rhabdomyolysis, and disruption of excitation-contraction coupling. Nevertheless, mechanisms that underlie t-volume changes are poorly understood. A multicompartment, history-independent computer model of rat skeletal muscle was developed to define the minimum conditions for t-volume stability. It was found that the t-system tends to swell due to net ionic fluxes from the ECF across the access resistance. However, a stable t-volume is possible when this is offset by a net efflux from the t-system to the cell and thence to the ECF, forming a net ion cycle ECF→t-system →sarcoplasm→ECF that ultimately depends on Na+/K+-ATPase activity. Membrane properties that maximise this circuit flux decrease t-volume, including PNa(t) > PNa(s), PK(t) < PK(s) and N(t) < N(s) (P, permeability; N, Na+/K+-ATPase density; (t), t-system membrane; (s), sarcolemma). Hydrostatic pressures, fixed charges and/or osmoles in the t-system can influence the magnitude of t-volume changes that result from alterations in this circuit flux. Using a parameter set derived from literature values where possible, this novel theory of t-volume was tested against data from previous experiments where t-volume was measured during manipulations of ECF composition. Predicted t-volume changes correlated satisfactorily. This present work provides a robust, unifying theoretical framework for understanding the determinants of t-volume.
dc.description.sponsorshipJAF was supported by a David Phillips Fellowship (BB/FO23863/1) awarded by the Biotechnology and Biological Sciences Research Council (UK). JS was supported by the Agency for Science, Technology and Research (Singapore) and a Caius Medical Association summer studentship from Gonville and Caius College, University of Cambridge.
dc.languageEnglishen
dc.language.isoenen
dc.publisherWiley
dc.rightsAttribution 2.0 UK: England & Wales
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/
dc.subjectskeletal muscleen
dc.subjecttransverse tubular (t-) systemen
dc.subjectcomputer modellingen
dc.titleThe determinants of transverse tubular volume in resting skeletal muscleen
dc.typeArticle
dc.description.versionThis is the final version. It was first published by Wiley at http://onlinelibrary.wiley.com/doi/10.1113/jphysiol.2014.281170/abstract.en
prism.endingPage5492
prism.publicationDate2014en
prism.publicationNameThe Journal of Physiologyen
prism.startingPage5477
prism.volume592en
dc.rioxxterms.funderBBSRC
dc.rioxxterms.projectidBB/FO23863/1
rioxxterms.versionofrecord10.1113/jphysiol.2014.281170en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2014-12-15en
dc.contributor.orcidFraser, James [0000-0002-6505-1883]
dc.identifier.eissn1469-7793
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBBSRC (BB/F023863/1)


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales