The time constant of the primary phase of pulmonary V˙O2 on-kinetics (τp ), which reflects muscle V˙O2 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 t0.63 to be achieved (analogous to τp , t0.63 is the time to reach 63% of the V˙O2 amplitude). A computer model of oxidative phosphorylation (OXPHOS) in skeletal muscle was used. Muscle t0.63 was near-linearly proportional to the difference in phosphocreatine (PCr) concentration between rest and work (ΔPCr). Of the two main factors that determine t0.63 , 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 t0.63 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 t0.63 below 10 s. Of note, the dependence of t0.63 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 τp . In summary, we postulate that the synergistic action of elevated OXPHOS activity and ESA intensity is responsible for extremely low τp (t0.63 ) observed in highly endurance-trained athletes
