Skeletal Muscle Regulatory Volume Response by Monocarboxylate Transporters to Increased Extracellular Lactate

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Leung, Matthew
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University of Guelph

The purpose of this thesis was to investigate the role of lactate in the regulatory volume response of mammalian skeletal muscle to hypertonic challenge-induced cell shrinkage. It was demonstrated that adult mice skeletal muscle single fibres responded to increased extracellular osmolarity in a dose-dependent manner when exposed to NaCl or sucrose challenge. This regulatory response to sucrose and NaCl however was abolished when cells were pre-treated with bumetanide, a specific sodium-potassium-chloride cotransport (NKCC) inhibitor, demonstrating that the NKCC is primarily responsible for eliciting a regulatory volume increase (RVI). When cells were exposed to NaLac treatment, bumetanide incubation did not significantly diminish the ability of the cells to recover volume. Furthermore, these cells lost less volume compared to NaCl or sucrose control. Inhibiting the single muscle fibres with either monocarboxylate transport (MCT) inhibitor phloretin or pCMBS resulted in significantly greater volume loss and impaired volume recovery. Combined MCT inhibition of phloretin or pCMBS with NKCC inhibition (bumetanide) led to unexpected findings, whereby the cells lost very little volume. These data suggest that while skeletal muscle fibres may utilize the NKCC to regulate volume, the ability for these cells to employ the most efficient means of volume regulation involves the inclusion of lactate as well via MCT uptake.

skeletal muscle, volume regulation, lactate