Human skeletal muscle and erythrocyte proteins involved in acid-base homeostasis: adaptations to chronic hypoxia

Juel, Carsten; Lundby, Carsten; Sander, Mikael; Calbet, José Antonio López; Hall, Gerrit van

doi:10.1111/j.1469-7793.2003.00639.x

Cited by 31 publications

(51 citation statements)

References 33 publications

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“…To date, however, the only published human study (79) has reported no changes in MCT1 and MCT4 content in European lowlanders after 2 and 8 wk at altitude (4,100 m, Bolivia), compared with muscle biopsy samples obtained at sea level. However, the authors did observe changes in sarcolemmal CA density, which may improve lactate and proton transport across the sarcolemma by regulating the pH gradient (see Cellular regulation: role of the pH gradient in regulating lactate transport activity during exercise?).…”

Section: Which Cellular and Molecular Signals/mechanisms Regulate Musmentioning

confidence: 94%

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Effects of acute and chronic exercise on sarcolemmal MCT1 and MCT4 contents in human skeletal muscles: current status

Thomas

Bishop

Lambert

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Two lactate/proton cotransporter isoforms (monocarboxylate transporters, MCT1 and MCT4) are present in the plasma (sarcolemmal) membranes of skeletal muscle. Both isoforms are symports and are involved in both muscle pH and lactate regulation. Accordingly, sarcolemmal MCT isoform expression may play an important role in exercise performance. Acute exercise alters human MCT content, within the first 24 h from the onset of exercise. The regulation of MCT protein expression is complex after acute exercise, since there is not a simple concordance between changes in mRNA abundance and protein levels. In general, exercise produces greater increases in MCT1 than in MCT4 content. Chronic exercise also affects MCT1 and MCT4 content, regardless of the initial fitness of subjects. On the basis of cross-sectional studies, intensity would appear to be the most important factor regulating exercise-induced changes in MCT content. Regulation of skeletal muscle MCT1 and MCT4 content by a variety of stimuli inducing an elevation of lactate level (exercise, hypoxia, nutrition, metabolic perturbations) has been demonstrated. Dissociation between the regulation of MCT content and lactate transport activity has been reported in a number of studies, and changes in MCT content are more common in response to contractile activity, whereas changes in lactate transport capacity typically occur in response to changes in metabolic pathways. Muscle MCT expression is involved in, but is not the sole determinant of, muscle H(+) and lactate anion exchange during physical activity.

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Section: Which Cellular and Molecular Signals/mechanisms Regulate Musmentioning

confidence: 94%

“…Different isoforms of NBC have also been detected and quantified in human (79,82) and rat (82,143) skeletal muscles. Furthermore, we have reported a significant correlation between NBC and MCT1 relative abundance (r ϭ 0.50, P Ͻ 0.01) in oxidative, but not glycolytic, rat muscle (143).…”

Section: Sarcolemmal Lactate/proton Cotransporters In Skeletal Musclementioning

confidence: 99%

Effects of acute and chronic exercise on sarcolemmal MCT1 and MCT4 contents in human skeletal muscles: current status

Thomas

Bishop

Lambert

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Combined, IHT may elicit increases in tissue perfusion capacity, enhance rates of phosphocreatine (PCr) resynthesis, and upregulate relevant gene expression (e.g., hypoxia-inducible factor-1 [HIF-1a], carbonic anhydrase III, monocarboxylate transporter-4 [MCT-4]) (16,23). In specific reference to muscle buffering capacity, hypoxic exposure has been shown to increase the content of lactate/H + cotransporters monocarboxylate(s) (MCT) 1 and 4, Na + -H + exchanger proteins, Na + -HCO 3 2 cotransporters, and concentrations of the enzyme carbonic anhydrase (17). This in turn may improve the lactate/H + transport system and internal pH regulation during exercise (17).…”

Section: Introductionmentioning

confidence: 99%

Differential Effect of Metabolic Alkalosis and Hypoxia on High-Intensity Cycling Performance

Flinn

Herbert²,

Graham³

et al. 2014

Journal of Strength and Conditioning Research

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Flinn, S, Herbert, K, Graham, K, and Siegler, JC. Differential effect of metabolic alkalosis and hypoxia on high-intensity cycling performance. J Strength Cond Res 28(10): 2852-2858, 2014-The purpose of this study was to investigate the effects of sodium bicarbonate (NaHCO 3 ) ingestion and acute hypoxic exposure on repeated bouts of high-intensity cycling to task failure. Twelve subjects completed 4 separate intermittent cycling bouts cycling bouts to task failure (120% peak power output for 30-second interspersed with 30-second active recovery) under the following conditions: normoxia (F I O 2 % at 20.93%) alkalosis (NA), normoxia placebo (NP), hypoxia (F I O 2 % at 14.7%) alkalosis (HA), and hypoxia placebo (HP). For the NA and HA trials, the buffer solution (0.3 g$kg 21 of NaHCO 3 ) was dispensed into gelatin capsules and consumed over 90 minutes with 1 L of water. Whole-blood acidbase findings demonstrated metabolic alkalosis in both NA and HA before exercise (HCO 3 2 : 32.8 6 1.8 mmol$L 21 ). Time to task failure was significantly impaired in the hypoxic conditions (NA: 199.1 6 62.3 seconds, NP: 183.8 6 45.0 seconds, HA: 127.8 6 27.9 seconds, HP: 133.3 6 28.7 seconds; p , 0.001; h 2 = 0.7). There was no difference between the HA and HP conditions (p = 0.41); however the 2 normoxic conditions approached significance with the NA condition on average resulting in approximately 15-second improvement in time to task failure (p = 0.09). These findings suggest that an acute decline in F I O 2 % consistent with hypoxic exposure is more inhibiting than metabolic acidosis during intermittent highintensity cycling to task failure. In application, the use of hypoxia and NaHCO 3 concurrently to improve performance under these conditions does not seem warranted. Figure 2. Time to task failure (s) for the 4 trial conditions (NA, NP, HA, and HP). Data are presented as mean 6 SD. *Significantly different from hypoxic conditions (p , 0.001). NA = normoxia alkalosis; NP = normoxia placebo; HA = hypoxia alkalosis; HP = hypoxia placebo.Figure 3. Individual performance data represented as responders, nonresponders, and negative responders. Journal of Strength and Conditioning Research the TM | www.nsca.com

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“…CAII binds to, and enhances the activity of various acid/base transporters like the chloride/bicarbonate exchanger AE1 (15,16), the sodium bicarbonate cotransporter NBCe1 (17,18), and the sodium/hydrogen exchanger NHE1 (19). In muscle cells, coexpression of CAII and acid/base-transporting proteins like NBC, NHE1, and also the MCTs have been found to be pivotal in acid/base homeostasis (20). In addition, it has been shown that extracellular carbonic anhydrase activity facilitates lactic acid transport in rat skeletal muscle fibers (21).…”

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confidence: 99%

Nonenzymatic Proton Handling by Carbonic Anhydrase II during H+-Lactate Cotransport via Monocarboxylate Transporter 1

Becker

Deitmer

2008

Journal of Biological Chemistry

105

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Carbonic anhydrase (CA) is a ubiquitous enzyme catalyzing the equilibration of carbon dioxide, protons, and bicarbonate. For several acid/base-coupled membrane carriers it has been shown that the catalytic activity of CA supports transport activity, an interaction coined "transport metabolon." We have reported that CA isoform II (CAII) enhances lactate transport activity of the monocarboxylate transporter isoform I (MCT1) expressed in Xenopus oocytes, which does not require CAII catalytic activity (Becker, H. M., Fecher-Trost, C., Hirnet, D., Sült-emeyer, D., and Deitmer, J. W. (2005) J. Biol. Chem. 280, 39882-39889). Coexpression of MCT1 with either wild type CAII or the catalytically inactive mutant CAII-V143Y similarly enhanced MCT1 activity, although injection of CAI or coexpression of an N-terminal mutant of CAII had no effect on MCT1 transport activity, demonstrating a specific, nonenzymatic action of CAII on lactate transport via MCT1. If the H ؉ gradient was set to dominate the rate of lactate transport by applying low concentrations of lactate at a high H ؉ concentration, the effect of CAII was largest. We tested the hypothesis of whether CAII helps to shuttle H ؉ along the inner face of the cell membrane by measuring the pH change with fluorescent dye in different areas of interest during focal lactate application. Intracellular pH shifts decayed from the focus of lactate application to more distant sites much less when CAII had been injected. We present a hypothetical model in which the effective movement of H ؉ into the bulk cytosol is increased by CAII, thus slowing the dissipation of the H ؉ gradient across the cell membrane, which drives MCT1 activity.Transport of acid/base equivalents across cell membranes plays a crucial role both for pH regulation and cellular import and export of metabolites. Many Na ϩ -dependent and Na ϩ -independent transport modes of metabolites (e.g. neurotransmitter substances) also transport H ϩ , OH Ϫ , or HCO 3 Ϫ as co-or counter-substrate. The energetic compounds lactate and pyruvate are primarily transported by monocarboxylate transporters (MCT) 2 in an electroneutral 1 proton-1 organic anion transport mode. Members of the MCT family, which belong to the human gene family SLC16 which comprise 14 isoforms, are expressed in most tissues, in particular those with a large energy consumption like muscle and brain (1, 2). In the brain MCT1 is located mainly in glial cells, where it facilitates the export of lactate, which is then taken up by neurons via the high affinity MCT2; thereby the two isoforms are believed to shuttle lactate from glial cells to neurons which seems to be pivotal for brain energy metabolism (3-6). In muscle, MCT1 is highly expressed in oxidative type I fibers, where it mediates import of lactate that is released by glycolytic muscle cells via MCT3 and MCT4 (7-9). MCT1, when expressed in Xenopus oocytes, operates with a K m value of 3.5 mM for lactate influx and of 6.4 mM for efflux of lactate. Both the rate and the amplitude of the lactate-induced ac...

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Human skeletal muscle and erythrocyte proteins involved in acid-base homeostasis: adaptations to chronic hypoxia

Cited by 31 publications

References 33 publications

Effects of acute and chronic exercise on sarcolemmal MCT1 and MCT4 contents in human skeletal muscles: current status

Effects of acute and chronic exercise on sarcolemmal MCT1 and MCT4 contents in human skeletal muscles: current status

Differential Effect of Metabolic Alkalosis and Hypoxia on High-Intensity Cycling Performance

Nonenzymatic Proton Handling by Carbonic Anhydrase II during H+-Lactate Cotransport via Monocarboxylate Transporter 1

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