Rates of oxidative ATP synthesis are not augmented beyond the pH threshold in human vastus lateralis muscles during a stepwise contraction protocol

Key points The oxygen cost of high-intensity exercise at power outputs above an individual's lactate threshold (LT) is greater than would be predicted by the linear oxygen consumption-power relationship observed below the LT. However, whether these augmentations are caused by an increased ATP cost of force generation (ATP(COST)) or an increased oxygen cost of ATP synthesis is unclear. We used P-31-MRS to measure changes in cytosolic [ADP] (intramyocellular marker of oxidative metabolism), oxidative ATP synthesis (ATP(OX)) and ATP(COST) during a 6-stage, stepwise knee extension protocol. ATP(COST) was unchanged across stages. The relationship between [ADP] and muscle power output was augmented at workloads above the pH threshold (pH(T); proxy for LT), whereas increases in ATP(OX) were attenuated. These results suggest the greater oxygen cost of contractions at workloads beyond the pH(T) is not caused by mechanisms that increase ATP(COST), but rather mechanisms that alter intrinsic mitochondrial function or capacity. Increases in skeletal muscle metabolism and oxygen consumption are linearly related to muscle power output for workloads below the lactate threshold (LT), but are augmented (i.e. greater rate of increase relative to workload) thereafter. Presently, it is unclear whether these metabolic augmentations are caused by increases in the ATP cost of force generation (ATP(COST)) or changes in the efficiency of mitochondrial oxygen consumption and oxidative ATP synthesis (ATP(OX)). To partition these two hypotheses in vivo, we used P-31-MRS to calculate slopes relating step-changes in muscle work to concurrent changes in cytosolic phosphates and ATP(OX) before and after the pH threshold (pH(T); used here as a proxy for LT) within the vastus lateralis muscle of eight young adults during a stepwise knee extension test. Changes in muscle phosphates and ATP(OX) were linearly related to workload below the pH(T). However, slopes above the pH(T) were greater for muscle phosphates (P < 0.05) and lower for ATP(OX) (P < 0.05) than were the slopes observed below the pH(T). The maximal capacity for ATP(OX) (V?max) and ADP-specific ATP(OX) also declined beyond the pH(T) (P < 0.05), whereas ATP(COST) was unchanged (P = 0.10). These results oppose the hypothesis that high-intensity contractions increase ATP(COST) and suggest that greater oxidative metabolism at workloads beyond the pH(T) is caused by mechanisms that affect intrinsic mitochondrial function or capacity, such as alterations in substrate selection or electron entry into the electron transport chain, temperature-mediated changes in mitochondrial permeability to protons, or stimulation of mitochondrial uncoupling by reactive oxygen species generation.

Automated summary

The study found that high-intensity exercise leads to increased oxygen consumption, potentially due to mechanisms affecting mitochondrial function or capacity.