Skeletal Muscle Regulatory Responses to Increased Extracellular Lactate

Mammalian skeletal muscle cells exhibit cell shrinkage followed by regulatory volume increase (RVI) in response to increases in extracellular osmolarity caused by addition of concentrated NaCl or sucrose. We hypothesized that increased extracellular sodium lactate would similarly result in a transient loss of cell volume, followed by RVI, and that the RVI would be more rapid and pronounced than that seen with NaCl due to entry of lactate into the cell. The present study measured the time course of change single fibre width in response to varied increases in extracellular NaCl or Na‐lactate. Adult mouse EDL single fibres were isolated using collagenase and incubated in DMEM prior to and during experimentation. Fibre images were obtained at 3–6 s intervals for up to 40 min. Fibre images were analyzed for width at 2 sites. Increased osmolarity resulted in a rapid decrease in fibre width, followed by RVI. The volume recovery was faster and more complete when [lactate] ≥20 mmol/L. There was a linear relationship between increases extracellular [lactate], cell shrinkage, and magnitude of RVI. It appears that the inward transport of lactate into skeletal muscle contributes, together with increased NKCC activity, to the RVI in mammalian skeletal muscle. Supported by NSERC of Canada.