Mechanisms underlying extremely fast muscle [Formula: see text] O(2) on‐kinetics in humans

The time constant of the primary phase of pulmonary [Formula: see text] O(2) on‐kinetics (τ (p)), which reflects muscle [Formula: see text] O(2) kinetics during moderate‐intensity exercise, is about 30 s in young healthy untrained individuals, while it can be as low as 8 s in endurance‐trained athletes. We aimed to determine the intramuscular factors that enable very low values of t (0.63) to be achieved (analogous to τ (p), t (0.63) is the time to reach 63% of the [Formula: see text] O(2) amplitude). A computer model of oxidative phosphorylation (OXPHOS) in skeletal muscle was used. Muscle t(0.63) was near‐linearly proportional to the difference in phosphocreatine (PCr) concentration between rest and work (ΔPCr). Of the two main factors that determine t(0.63), a huge increase in either OXPHOS activity (six‐ to eightfold) or each‐step activation (ESA) of OXPHOS intensity (>3‐fold) was needed to reduce muscle t (0.63) from the reference value of 29 s (selected to represent young untrained subjects) to below 10 s (observed in athletes) when altered separately. On the other hand, the effect of a simultaneous increase of both OXPHOS activity and ESA intensity required only a twofold elevation of each to decrease t (0.63) below 10 s. Of note, the dependence of t (0.63) on OXPHOS activity and ESA intensity is hyperbolic, meaning that in trained individuals a large increase in OXPHOS activity and ESA intensity are required to elicit a small reduction in τ (p). In summary, we postulate that the synergistic action of elevated OXPHOS activity and ESA intensity is responsible for extremely low τ (p) (t (0.63)) observed in highly endurance‐trained athletes.