The determinants of transverse tubular volume in resting skeletal muscle.
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 are thought to contribute to fatigue, rhabdomyolysis and disruption of excitation-contraction coupling. However, 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 maximize 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. The present work provides a robust, unifying theoretical framework for understanding the determinants of t-volume.
Physiological Laboratory, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.
Jingwei
J
Sim
Physiological Laboratory, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK jaf21@cam.ac.uk.
James A
JA
Fraser
D000818:Animals; D005110:Extracellular Space / Q000378:metabolism; D017136:Ion Transport; D008564:Membrane Potentials; D008954:Models, Biological; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D051381:Rats; D012508:Sarcolemma / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D000254:Sodium-Potassium-Exchanging ATPase