The determinants of transverse tubular volume in resting skeletal muscle
The Journal of Physiology
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Sim, J., & Fraser, J. (2014). The determinants of transverse tubular volume in resting skeletal muscle. The Journal of Physiology, 592 5477-5492. https://doi.org/10.1113/jphysiol.2014.281170
The 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.
skeletal muscle, transverse tubular (t-) system, computer modelling
JAF 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.
External DOI: https://doi.org/10.1113/jphysiol.2014.281170
This record's URL: https://www.repository.cam.ac.uk/handle/1810/246220
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/