Bioenergetics and ATP Synthesis during Exercise: Role of Group III/IV Muscle Afferents

Abstract

Purpose: The purpose of this study was to investigate the role of the group III/IV muscle afferents in the bioenergetics of exercising skeletal muscle beyond constraining the magnitude of metabolic perturbation.

Methods: Eight healthy men performed intermittent isometric knee-extensor exercise to task failure at ~58% maximal voluntary contraction under control conditions (CTRL) and with lumbar intrathecal fentanyl to attenuate group III/IV leg muscle afferents (FENT). Intramuscular concentrations of phosphocreatine (PCr), inorganic phosphate (Pi), diprotonated phosphate (H2PO4), adenosine triphosphate (ATP), and pH were determined using phosphorous magnetic resonance spectroscopy (P-MRS).

Results: The magnitude of metabolic perturbation was significantly greater in FENT compared with CTRL for [Pi] (37.8 ± 16.8 vs 28.6 ± 8.6 mM), [H2PO4] (24.3 ± 12.2 vs 17.9 ± 7.1 mM), and [ATP] (75.8% ± 17.5% vs 81.9% ± 15.8% of baseline), whereas there was no significant difference in [PCr] (4.5 ± 2.4 vs 4.4 ± 2.3 mM) or pH (6.51 ± 0.10 vs 6.54 ± 0.14). The rate of perturbation in [PCr], [Pi], [H2PO4], and pH was significantly faster in FENT compared with CTRL. Oxidative ATP synthesis was not significantly different between conditions. However, anaerobic ATP synthesis, through augmented creatine kinase and glycolysis reactions, was significantly greater in FENT than in CTRL, resulting in a significantly greater ATP cost of contraction (0.049 ± 0.016 vs 0.038 ± 0.010 mM·min·N).

Conclusion: Group III/IV muscle afferents not only constrain the magnitude of perturbation in intramuscular Pi, H2PO4, and ATP during small muscle mass exercise but also seem to play a role in maintaining efficient skeletal muscle contractile function in men.

Figure 1. Force development and exercise tolerance during high-intensity intermittent isometric single-leg knee-extensor exercise

Subjects were required to attain a target force during each 3 s contraction and the force integral of each contraction was calculated during control (CTRL) and fentanyl (FENT) conditions. Values are mean ± SEM for each contraction up to the last common time point prior to task failure for all participants and at task failure. The time to task failure, force integral per contraction, and the cumulative force integral were not significantly different between experimental conditions.

Figure 2. Intramuscular metabolic perturbation during high-intensity intermittent isometric single-leg knee-extensor exercise

Intramuscular metabolite concentrations were obtained using ³¹P-MRS during control (CTRL) and fentanyl (FENT) conditions. Main effects and interactions are indicated in the graphs. Values are mean ± SEM for each contraction up to the last common time point prior to task failure for all participants and at task failure. † significantly different from CTRL at specific time point.

Figure 3. Adenosine triphosphate (ATP) synthesis rates and ATP cost of contraction during high-intensity intermittent isometric single-leg knee-extensor exercise

The rate of ATP synthesis through the creatine kinase reaction (ATP_CK), anaerobic glycolysis (ATP_GLY), cumulative anaerobic metabolism (ATP_ANA), oxidative phosphorylation (ATP_OX), and total ATPase rate (ATP_TOTAL) and the ATP cost of contraction for the 1^st and final minutes of exercise between fentanyl (FENT) and control (CTRL) conditions. Values are mean ± SEM. * significant main effect for condition, † significantly different from CTRL, and ‡ significantly different from 1^st min.