Regulatory volume response to increased extracellular lactate via monocarboxylate transporters in mammalian skeletal muscle

Mammalian skeletal muscle cells regulate volume in response to changes in extracellular osmolarity. As a result of increased osmolarity, the rate of regulatory volume increase (RVI) is hypothesized to occur more rapidly in the presence of lactate− anions, as opposed to Cl− anion, since influx of lactate− via monocarboxylate transporters (MCTs) should increase the rate that intracellular/extracellular osmolarity equilibrate. We investigated the role of lactate− in RVI, by way of the MCT. Adult mouse peroneous muscle fibres were isolated and width measurements obtained at 2 sites per fibre, every 5–10 seconds for 30 min, in response to increased extracellular osmolarity via NaCl or NaLactate treatment. The extracellular changes in osmolarity occurred in presence/absence of NKCC (bumetanide) and MCT (pCMBS and phloretin) inhibitors. Increasing extracellular osmolarity caused rapid cell shrinkage, with subsequent recovery to baseline volume. Volume loss for NaLactate was less than NaCl treatment. Bumetanide caused greater peak volume decrease vs. control. MCT inhibition by pCMBS or phloretin also showed a more pronounced volume reduction vs. control, however the magnitude of decrease was greater in contrast to NKCC inhibition alone. In summary, results suggest the MCT plays a notable role in facilitating RVI via lactate transport in the optimal response of skeletal muscle cells to undergo volume recovery. Supported by NSERC of Canada