Validity and accuracy of calculating oxidative ATP synthesis in vivo during high‐intensity skeletal muscle contractions

2020 ◽  
Vol 33 (11) ◽  
Author(s):  
Miles F. Bartlett ◽  
Liam F. Fitzgerald ◽  
Rajakumar Nagarajan ◽  
Jane A. Kent
Keyword(s):  
Skeletal Muscle ◽  
High Intensity ◽  
Atp Synthesis ◽  
Muscle Contractions

A malonyl-CoA fuel-sensing mechanism in muscle: effects of insulin, glucose, and denervation

1995 ◽  
Vol 269 (2) ◽  
pp. E283-E289 ◽  
Author(s):  
A. K. Saha ◽  
T. G. Kurowski ◽  
N. B. Ruderman
Keyword(s):  
Skeletal Muscle ◽  
Plasma Insulin ◽  
Contractile Activity ◽  
High Plasma ◽  
Muscle Contractions ◽  
Glucose Levels ◽  
Malonyl Coa ◽  
Ad Libitum ◽  
Sciatic Nerve Stimulation

Increases in the concentration of malonyl-CoA in skeletal muscle have been observed in the KKAy mouse, an obese rodent with high plasma insulin and glucose levels [Saha et al. Am. J. Physiol. 267 (Endocrinol. Metab. 30): E95-E101, 1994]. To assess whether insulin and glucose directly regulate malonyl-CoA in muscle, soleus muscles from young rats were incubated with insulin and glucose at various concentrations, and their content of malonyl-CoA was determined. In addition, the effect on malonyl-CoA of denervation and electrically induced muscle contractions was assessed. The concentration of malonyl-CoA in the soleus, taken directly from a rat fed ad libitum, was 2.0 +/- 0.2 nmol/g. In muscles incubated for 20 min in a medium devoid of added insulin and glucose, the concentration was decreased to 0.8 +/- 0.2 nmol/g. When the medium contained 0.5, 7.5, or 30 mM glucose, malonyl-CoA levels were 1.3 +/- 0.1, 1.8 +/- 0.1, or 2.4 +/- 0.2 nmol/g, respectively, in the absence of insulin and 1.7 +/- 0.1, 4.6 +/- 0.3, or 5.5 +/- 0.6 nmol/g in its presence (10 mU/ml). Compared with its level in a control muscle, the concentration of malonyl-CoA was increased threefold in the soleus 6-8 h after denervation and remained twofold higher for > or = 48 h. In contrast, muscle contractions induced by sciatic nerve stimulation, in vivo, acutely decreased the concentration of malonyl-CoA by 30-35%. The results indicate that insulin and glucose, and probably contractile activity, regulate the concentration of malonyl-CoA in muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Visualization of Mitochondrial Ca2+ Signals in Skeletal Muscle of Zebrafish Embryos with Bioluminescent Indicators

2019 ◽  
Vol 20 (21) ◽  
pp. 5409 ◽  
Author(s):  
Manuel Vicente ◽  
Jussep Salgado-Almario ◽  
Joaquim Soriano ◽  
Miguel Burgos ◽  
Beatriz Domingo ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Contractions ◽  
Zebrafish Embryos ◽  
Mitochondrial Matrix ◽  
Mitochondrial Calcium Uniporter ◽  
Calcium Uniporter ◽  
Skeletal Muscle Contraction ◽  
Spatio Temporal ◽  
Mitochondrial Uncoupler

Mitochondria are believed to play an important role in shaping the intracellular Ca2+ transients during skeletal muscle contraction. There is discussion about whether mitochondrial matrix Ca2+ dynamics always mirror the cytoplasmic changes and whether this happens in vivo in whole organisms. In this study, we characterized cytosolic and mitochondrial Ca2+ signals during spontaneous skeletal muscle contractions in zebrafish embryos expressing bioluminescent GFP-aequorin (GA, cytoplasm) and mitoGFP-aequorin (mitoGA, trapped in the mitochondrial matrix). The Ca2+ transients measured with GA and mitoGA reflected contractions of the trunk observed by transmitted light. The mitochondrial uncoupler FCCP and the inhibitor of the mitochondrial calcium uniporter (MCU), DS16570511, abolished mitochondrial Ca2+ transients whereas they increased the frequency of cytosolic Ca2+ transients and muscle contractions, confirming the subcellular localization of mitoGA. Mitochondrial Ca2+ dynamics were also determined with mitoGA and were found to follow closely cytoplasmic changes, with a slower decay. Cytoplasmic Ca2+ kinetics and propagation along the trunk and tail were characterized with GA and with the genetically encoded fluorescent Ca2+ indicator, Twitch-4. Although fluorescence provided a better spatio-temporal resolution, GA was able to resolve the same kinetic parameters while allowing continuous measurements for hours.

scholarly journals Complex I is bypassed during high intensity exercise

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Avlant Nilsson ◽  
Elias Björnson ◽  
Mikael Flockhart ◽  
Filip J. Larsen ◽  
Jens Nielsen
Keyword(s):  
High Intensity ◽  
Complex I ◽  
Atp Synthesis ◽  
Metabolic Model ◽  
High Intensity Exercise ◽  
Whole Body ◽  
Synthesis Rate ◽  
Proteomics Data ◽  
Exercise Tests

Abstract Human muscles are tailored towards ATP synthesis. When exercising at high work rates muscles convert glucose to lactate, which is less nutrient efficient than respiration. There is hence a trade-off between endurance and power. Metabolic models have been developed to study how limited catalytic capacity of enzymes affects ATP synthesis. Here we integrate an enzyme-constrained metabolic model with proteomics data from muscle fibers. We find that ATP synthesis is constrained by several enzymes. A metabolic bypass of mitochondrial complex I is found to increase the ATP synthesis rate per gram of protein compared to full respiration. To test if this metabolic mode occurs in vivo, we conduct a high resolved incremental exercise tests for five subjects. Their gas exchange at different work rates is accurately reproduced by a whole-body metabolic model incorporating complex I bypass. The study therefore shows how proteome allocation influences metabolism during high intensity exercise.

scholarly journals In vivo imaging of intracellular Ca 2+ after muscle contractions and direct Ca 2+ injection in rat skeletal muscle in diabetes

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Hiroaki Eshima ◽  
Yoshinori Tanaka ◽  
Takashi Sonobe ◽  
Tadakatsu Inagaki ◽  
David C Poole ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
In Vivo Imaging ◽  
Muscle Contractions ◽  
Rat Skeletal Muscle ◽  
Intracellular Ca

In Vivo Skeletal Muscle Oxidative and Glycolytic ATP Synthesis in Young and Older Adults

2006 ◽  
Vol 38 (Supplement) ◽  
pp. S521
Author(s):  
Ian R. Lanza ◽  
Douglas E. Befroy ◽  
Danielle M. Wigmore ◽  
Jane A. Kent-Braun
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Atp Synthesis ◽  
Glycolytic Atp

scholarly journals Efficiency of human skeletal muscle in vivo: comparison of isometric, concentric, and eccentric muscle action

1997 ◽  
Vol 83 (3) ◽  
pp. 867-874 ◽  
Author(s):  
T. W. Ryschon ◽  
M. D. Fowler ◽  
R. E. Wysong ◽  
A.-R. Anthony ◽  
R. S. Balaban
Keyword(s):  
Skeletal Muscle ◽  
Steady State ◽  
Production Rate ◽  
Human Skeletal Muscle ◽  
Atp Synthesis ◽  
High Energy ◽  
High Energy Phosphates ◽  
Muscle Action ◽  
Atp Production

Ryschon, T. W., Fowler, R. E. Wysong, A.-R. Anthony, and R. S. Balaban. Efficiency of human skeletal muscle in vivo: comparison of isometric, concentric, and eccentric muscle action. J. Appl. Physiol. 83(3): 867–874, 1997.—The purpose of this study was to estimate the efficiency of ATP utilization for concentric, eccentric, and isometric muscle action in the human tibialis anterior and extensor digitorum longus in vivo. A dynamometer was used to quantitate muscle work, or tension, while simultaneous 31P-nuclear magnetic resonance data were collected to monitor ATP, phosphocreatine, inorganic phosphate, and pH. The relative efficiency of the actions was estimated in two ways: steady-state effects on high-energy phosphates and a direct comparison of ATP synthesis rates with work. In the steady state, the cytosolic free energy dropped to the lowest value with concentric activity, followed by eccentric and isometric action for comparative muscle tensions. Estimates of ATP synthesis rates revealed a mechanochemical efficiency [i.e., ATP production rate/work (both in J/s)] of 15.0 ± 1.3% in concentric and 34.7 ± 6.1% in eccentric activity. The estimated maximum ATP production rate was highest in concentric action, suggesting an activation of energy metabolism under these conditions. By using direct measures of metabolic strain and ATP turnover, these data demonstrate a decreasing metabolic efficiency in human muscle action from isometric, to eccentric, to concentric action.

scholarly journals Magnitude and control of mitochondrial sensitivity to ADP

2009 ◽  
Vol 297 (3) ◽  
pp. E774-E784 ◽  
Author(s):  
Jeroen A. L. Jeneson ◽  
Joep P. J. Schmitz ◽  
Nicole M. A. van den Broek ◽  
Natal A. W. van Riel ◽  
Peter A. J. Hilbers ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
In Silico ◽  
Adenine Nucleotide ◽  
Atp Synthesis ◽  
Model Parameters ◽  
Kinetic Properties ◽  
Mitochondrial Enzymes ◽  
Concentration Changes ◽  
Multiparametric Sensitivity Analysis

The transduction function for ADP stimulation of mitochondrial ATP synthesis in skeletal muscle was reconstructed in vivo and in silico to investigate the magnitude and origin of mitochondrial sensitivity to cytoplasmic ADP concentration changes. Dynamic in vivo measurements of human leg muscle phosphocreatine (PCr) content during metabolic recovery from contractions were performed by 31P-NMR spectroscopy. The cytoplasmic ADP concentration ([ADP]) and rate of oxidative ATP synthesis (Jp) at each time point were calculated from creatine kinase equilibrium and the derivative of a monoexponential fit to the PCr recovery data, respectively. Reconstructed [ADP]-Jp relations for individual muscles containing more than 100 data points were kinetically characterized by nonlinear curve fitting yielding an apparent kinetic order and ADP affinity of 1.9 ± 0.2 and 0.022 ± 0.003 mM, respectively (means ± SD; n = 6). Next, in silico [ADP]-Jp relations for skeletal muscle were generated using a computational model of muscle oxidative ATP metabolism whereby model parameters corresponding to mitochondrial enzymes were randomly changed by 50–150% to determine control of mitochondrial ADP sensitivity. The multiparametric sensitivity analysis showed that mitochondrial ADP ultrasensitivity is an emergent property of the integrated mitochondrial enzyme network controlled primarily by kinetic properties of the adenine nucleotide translocator.

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