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Inward Flux of Lactate(-) through Monocarboxylate Transporters Contributes to Regulatory Volume Increase in Mouse Muscle Fibres

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, increas...

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Autores principales: Lindinger, Michael I., Leung, Matthew J., Hawke, Thomas J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3871844/
https://www.ncbi.nlm.nih.gov/pubmed/24376811
http://dx.doi.org/10.1371/journal.pone.0084451
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author Lindinger, Michael I.
Leung, Matthew J.
Hawke, Thomas J.
author_facet Lindinger, Michael I.
Leung, Matthew J.
Hawke, Thomas J.
author_sort Lindinger, Michael I.
collection PubMed
description 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.
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spelling pubmed-38718442013-12-27 Inward Flux of Lactate(-) through Monocarboxylate Transporters Contributes to Regulatory Volume Increase in Mouse Muscle Fibres Lindinger, Michael I. Leung, Matthew J. Hawke, Thomas J. PLoS One Research Article 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. Public Library of Science 2013-12-23 /pmc/articles/PMC3871844/ /pubmed/24376811 http://dx.doi.org/10.1371/journal.pone.0084451 Text en © 2013 Lindinger et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lindinger, Michael I.
Leung, Matthew J.
Hawke, Thomas J.
Inward Flux of Lactate(-) through Monocarboxylate Transporters Contributes to Regulatory Volume Increase in Mouse Muscle Fibres
title Inward Flux of Lactate(-) through Monocarboxylate Transporters Contributes to Regulatory Volume Increase in Mouse Muscle Fibres
title_full Inward Flux of Lactate(-) through Monocarboxylate Transporters Contributes to Regulatory Volume Increase in Mouse Muscle Fibres
title_fullStr Inward Flux of Lactate(-) through Monocarboxylate Transporters Contributes to Regulatory Volume Increase in Mouse Muscle Fibres
title_full_unstemmed Inward Flux of Lactate(-) through Monocarboxylate Transporters Contributes to Regulatory Volume Increase in Mouse Muscle Fibres
title_short Inward Flux of Lactate(-) through Monocarboxylate Transporters Contributes to Regulatory Volume Increase in Mouse Muscle Fibres
title_sort inward flux of lactate(-) through monocarboxylate transporters contributes to regulatory volume increase in mouse muscle fibres
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3871844/
https://www.ncbi.nlm.nih.gov/pubmed/24376811
http://dx.doi.org/10.1371/journal.pone.0084451
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