Regulation of skeletal muscle metabolism : supply and demand
Creators: name: Di Maria, Carla A.
Publisher: name: University Of Tasmania
Year: 2023

description: Regulation of Skeletal Muscle Metabolism ‚ÄövÑvÆ Supply and Demand This thesis examines the regulation of skeletal muscle metabolism under resting conditions. Previous studies have shown that vasoconstrictors stimulate [type A] or inhibit [type B] metabolism of the constant flow perfused rat hindlimb. There is evidence that this may be due to redistribution of blood flow between the two vascular pathways in skeletal muscle, either increasing [type A] or decreasing [type B] the extent of nutritive perfusion. It is not clear if enhanced nutritive perfusion and therefore enhanced oxygen delivery is enough to account for the observed increase in metabolism with type A vasoconstrictors. It has been proposed that a cellular thermogenic mechanism is activated in addition to redistribution. The identity of this mechanism is not clear. A number of possibilities are explored. The effects of varied oxygen delivery on hindlimb oxygen uptake were examined. Flow was maintained at a constant level while arterial oxygen content was varied. Three independent methods (1-MX metabolism, microdialysis and laser doppler flowmetry) were utilized to rigorously monitor redistribution. A positive relationship between oxygen delivery and hindlimb oxygen uptake was detected, independent of redistribution. Cellular ATP levels were maintained, though PCr stores were depleted at low oxygen delivery. Lactate efflux increased, but was not considered great enough to fully compensate for diminished ATP production from aerobic sources. In this regard, the perfused rat hindlimb may be considered as an oxygen conforming tissue. Thus oxygen delivery is a key determinant of skeletal muscle metabolic rate, and type A vasoconstrictors may effectively enhance oxygen delivery by improving nutritive perfusion. Mechanisms accounting for increased oxygen consumption during enhanced delivery were explored. The roles of sodium cycling and accompanying Na+/K+- ATPase pump activity were assessed. Comparisons were made between type A vasoconstrictors and the sodium channel labilizer veratridine in both skeletal and cardiac muscle. In perfused skeletal muscle both vasoconstrictor- and veratridinemediated metabolism were blocked by the sodium pump inhibitor ouabain, however vasoconstrictor-mediated metabolism was resistant to sodium channel inhibition with tetrodotoxin (TTX). The same TTX-resistant vasoconstrictor-thermogenic effect was absent from perfused arrested rat heart, possibly due to differences in vascular anatomy. Intracellular recording techniques failed to detect any change in skeletal fiber membrane potential during type A vasoconstrictor infusion, but did detect changes with veratridine. In summary the data supports the notion that metabolic demand (sodium load with veratridine) can stimulate hindlimb metabolism. However, there was no evidence for type A vasoconstrictor mediated changes in muscle sodium cycling, Na+/K+-ATPase activity, or membrane depolarization. Oxygen consumption of resting skeletal muscle is largely controlled by oxygen delivery, whether this is by changes in bulk flow or flow redistribution. Cellular thermogenic mechanisms may well be activated in response to increased oxygen delivery, though sodium cycling/pumping is no longer a candidate.