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Validity and accuracy of calculating oxidative ATP synthesis in vivo during high‐intensity skeletal muscle contractions
Author(s) -
Bartlett Miles F.,
Fitzgerald Liam F.,
Nagarajan Rajakumar,
Kent Jane A.
Publication year - 2020
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.4381
Subject(s) - phosphocreatine , atp synthase , oxidative phosphorylation , cytosol , adenosine triphosphate , chemistry , chemiosmosis , coupling (piping) , michaelis–menten kinetics , biophysics , biochemistry , enzyme , biology , energy metabolism , materials science , enzyme assay , endocrinology , metallurgy
Several methods have been developed for using 31 P‐MRS to calculate rates of oxidative ATP synthesis (ATP OX ) during muscular contractions based on assumptions that (1) the ATP cost of force generation (ATP COST ) remains constant or (2) Michaelis‐Menten coupling between cytosolic ADP and ATP OX does not change. However, growing evidence suggests that one, or both, of these assumptions are invalid during high‐intensity fatigue protocols. Consequently, there is a need to examine the validity and accuracy of traditional ATP OX calculation methods under these conditions. To address this gap, we measured phosphate concentrations and pH in the vastus lateralis muscle of nine young adults during four rest‐contraction‐recovery trials lasting 24, 60, 120, and 240 s. The initial velocity of phosphocreatine resynthesis ( V iPCr ) following each trial served as the criterion measure of ATP OX because this method makes no assumptions of constant ATP COST or Michaelis‐Menten coupling between changes in cytosolic ADP and ATP OX . Subsequently, we calculated ATP OX throughout the 240 s trial using several traditional calculation methods and compared estimations of ATP OX from each method with time‐matched measurements of V iPCr . Method 1, which assumes that ATP COST does not change, was able to model changes in V iPCr over time, but showed poor accuracy for predicting V iPCr across a wide range of ATP OX values. In contrast, Michaelis‐Menten methods, which assume that the relationship between changes in cytosolic ADP and ATP OX remains constant, were invalid because they could not model the decline in V iPCr . However, adjusting these Michaelis‐Menten methods for observed changes in maximal ATP OX capacity (i.e., V max ) permitted modeling of the decline in V iPCr and markedly improved accuracy. The results of these comprehensive analyses demonstrate that valid, accurate measurements of ATP OX can be obtained during high‐intensity contractions by adjusting Michaelis‐Menten ATP OX calculations for changes in V max observed from baseline to post‐fatigue.