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dc.contributor.authorSim, Jingweien
dc.contributor.authorFraser, Jamesen
dc.identifier.citationThe Journal of Physiology 592: 5477–5492. doi: 10.1113/jphysiol.2014.281170en
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.rightsAttribution 2.0 UK: England & Wales
dc.subjectskeletal muscleen
dc.subjecttransverse tubular (t-) systemen
dc.subjectcomputer modellingen
dc.titleThe determinants of transverse tubular volume in resting skeletal muscleen
dc.description.versionThis is the final version. It was first published by Wiley at
prism.publicationNameThe Journal of Physiologyen
dc.contributor.orcidFraser, James [0000-0002-6505-1883]
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