Skeletal muscle bioenergetics during all-out exercise: mechanistic insight into the oxygen uptake slow component and neuromuscular fatigue

Abstract

Although all-out exercise protocols are commonly used, the physiological mechanisms underlying all-out exercise performance are still unclear, and an in-depth assessment of skeletal muscle bioenergetics is lacking. Therefore, phosphorus magnetic resonance spectroscopy (³¹P-MRS) was utilized to assess skeletal muscle bioenergetics during a 5-min all-out intermittent isometric knee-extensor protocol in eight healthy men. Metabolic perturbation, adenosine triphosphate (ATP) synthesis rates, ATP cost of contraction, and mitochondrial capacity were determined from intramuscular concentrations of phosphocreatine (PCr), inorganic phosphate (P_i), diprotonated phosphate ([Formula: see text]), and pH. Peripheral fatigue was determined by exercise-induced alterations in potentiated quadriceps twitch force (Q_tw) evoked by supramaximal electrical femoral nerve stimulation. The oxidative ATP synthesis rate (ATP_OX) attained and then maintained peak values throughout the protocol, despite an ~63% decrease in quadriceps maximal force production. ThusATP_OX normalized to force production (ATP_OX gain) significantly increased throughout the exercise (1st min: 0.02 ± 0.01, 5th min: 0.04 ± 0.01 mM·min^-1·N^-1), as did the ATP cost of contraction (1st min: 0.048 ± 0.019, 5th min: 0.052 ± 0.015 mM·min^-1·N^-1). Additionally, the pre- to postexercise change in Q_tw (-52 ± 26%) was significantly correlated with the exercise-induced change in intramuscular pH (r = 0.75) and [Formula: see text] concentration (r = 0.77). In conclusion, the all-out exercise protocol utilized in the present study elicited a "slow component-like" increase in intramuscular ATP_OX gain as well as a progressive increase in the phosphate cost of contraction. Furthermore, the development of peripheral fatigue was closely related to the perturbation of specific fatigue-inducing intramuscular factors (i.e., pH and [Formula: see text] concentration).NEW & NOTEWORTHY The physiological mechanisms and skeletal muscle bioenergetics underlying all-out exercise performance are unclear. This study revealed an increase in oxidative ATP synthesis rate gain and the ATP cost of contraction during all-out exercise. Furthermore, peripheral fatigue was related to the perturbation in pH and deprotonated phosphate ion. These findings support the concept that the oxygen uptake slow component arises from within active skeletal muscle and that skeletal muscle force generating capacity is linked to the intramuscular metabolic milieu.

Keywords: ATP cost; ATP synthesis; magnetic resonance spectroscopy; muscle metabolism; neuromuscular fatigue.

Fig. 1.

Force development during the 5-min all-out intermittent isometric single-leg knee-extensor protocol. Subjects performed a series of 60 intermittent maximal voluntary contractions (3-s contraction, 2-s relaxation) over 5 min. Peak force and mean force were determined per maximal voluntary contraction.

Fig. 2.

Intramuscular metabolic perturbation during the 5-min all-out intermittent isometric single-leg knee-extensor protocol. Intramuscular metabolite concentrations were determined with phosphorus magnetic resonance spectroscopy. †Significantly different from baseline.

Fig. 3.

Relationship between quadriceps fatigue and intramuscular metabolites. Data are expressed as % difference from baseline to end exercise for intramuscular pH and hydrogen ion ([H⁺]), inorganic phosphate ([P_i]), and diprotonated phosphate ([${\mathrm{H}}_{\mathrm{2}}\mathrm{P}{\mathrm{O}}_{\mathrm{4}}^{\mathrm{-}}$]) concentrations vs. preexercise-to-postexercise % difference for the potentiated quadriceps twitch force (Q_tw).

Fig. 4.

Adenosine triphosphate (ATP) synthesis rates and ATP cost of contraction during 5-min all-out intermittent isometric single-leg knee-extensor protocol. Rate of ATP synthesis through creatine kinase reaction (ATP_CK), anaerobic glycolysis (ATP_GLY), cumulative anaerobic metabolism (ATP_ANA), and oxidative phosphorylation (ATP_OX), total ATPase rate (ATP_TOTAL), and ATP cost of contraction were determined for each minute of exercise. Significantly different: †from 1st minute, ‡from 2nd minute, *from 3rd minute (P < 0.05).

Fig. 5.

Contribution of oxidative and anaerobic adenosine triphosphate (ATP) production during 5-min all-out intermittent isometric single-leg knee-extension protocol. Rates of ATP synthesis through oxidative phosphorylation (ATP_OX) and anaerobic metabolism (ATP_ANA) are expressed relative to total ATPase rate (ATP_TOTAL). Significantly different: *between conditions, †from 1st minute, ‡from 2nd minute (P < 0.05).

Fig. 6.

Oxidative and anaerobic adenosine triphosphate (ATP) gain during 5-min all-out intermittent isometric single-leg knee-extension protocol. Gains were determined as the rate of ATP synthesis through oxidative phosphorylation (ATP_OX) and anaerobic metabolism (ATP_ANA) normalized to the integrated force. Significantly different: †from 1st minute, ‡from 2nd minute, *from 3rd minute (P < 0.05).