Mechanisms underlying extremely fast muscle V̇O₂ on-kinetics in humans

The time constant of the primary phase of pulmonary V̇O₂ on‐kinetics (τp), which reflects muscle V̇O₂ 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 V̇O₂ 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.