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

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

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dc.contributor.advisor Michael, Lindinger
dc.contributor.author Leung, Matthew
dc.date 2011-12-28
dc.date.accessioned 2011-12-08T20:47:11Z
dc.date.available 2011-12-08T20:47:11Z
dc.date.issued 2011-12-08
dc.identifier.uri http://hdl.handle.net/10214/3175
dc.description.abstract 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. en_US
dc.description.sponsorship NSERC en_US
dc.language.iso en en_US
dc.subject skeletal muscle en_US
dc.subject volume regulation en_US
dc.subject lactate en_US
dc.title Skeletal Muscle Regulatory Volume Response by Monocarboxylate Transporters to Increased Extracellular Lactate en_US
dc.type Thesis en_US
dc.degree.programme Human Health and Nutritional Sciences en_US
dc.degree.name Master of Science en_US
dc.degree.department Department of Human Health and Nutritional Sciences en_US


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