Mechanisms underlying extremely fast muscle V ˙ O 2 on‐kinetics in humans

The time constant of the primary phase of pulmonary V ˙ O 2 on‐kinetics ( τ p ), which reflects muscle V ˙ 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 V ˙ 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 ( PC r) concentration between rest and work (Δ PC r). 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.