Inward Flux of Lactate- through Monocarboxylate Transporters Contributes to Regulatory Volume Increase in Mouse Muscle FibresReport as inadecuate




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Mouse and rat skeletal muscles are capable of a regulatory volume increase RVI after they shrink volume loss resultant from exposure to solutions of increased osmolarity and that this RVI occurs mainly by a Na-K-Cl-Cotransporter NKCC - dependent mechanism. With high-intensity exercise, increased extracellular osmolarity is accompanied by large increases in extracellular lactate-. We hypothesized that large increases in lactate- and osmolarity augment the NKCC-dependent RVI response observed with a NaCl or sucrose - induced increase in osmolarity alone; a response that is dependent on lactate- influx through monocarboxylate transporters MCTs. Single mouse muscle fibres were isolated and visualized under light microscopy under varying osmolar conditions. When solution osmolarity was increased by adding NaLac by 30 or 60 mM, fibres lost significantly less volume and regained volume sooner compared to when NaCl was used. Phloretin MCT1 inhibitor accentuated the volume loss compared to both NaLac controls, supporting a role for MCT1 in the RVI response in the presence of elevated lactate-. Inhibition of MCT4 with pCMBS resulted in a volume loss, intermediate to that seen with phloretin and NaLac controls. Bumetanide NKCC inhibitor, in combination with pCMBS, reduced the magnitude of volume loss, but volume recovery was complete. While combined phloretin-bumetanide also reduced the magnitude of the volume loss, it also largely abolished the cell volume recovery. In conclusion, RVI in skeletal muscle exposed to raised tonicity and lactate- is facilitated by inward flux of solute by NKCC- and MCT1-dependent mechanisms. This work demonstrates evidence of a RVI response in skeletal muscle that is facilitated by inward flux of solute by MCT-dependent mechanisms. These findings further expand our understanding of the capacities for skeletal muscle to volume regulate, particularly in instances of raised tonicity and lactate- concentrations, as occurs with high intensity exercise.



Author: Michael I. Lindinger , Matthew J. Leung, Thomas J. Hawke

Source: http://plos.srce.hr/



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