Methods
Eight untrained subjects performed VO₂peak and lactate threshold (LT) tests prior to and following a 6-week training program. Prior to and following the training period biopsies were taken from the v. lateralis. Muscle fiber bundles were separated and the sarcolemma was chemically permeabilized (skinned). Skinned fiber oxygen consumption was measured (prior to and following incubation in a ROS generating solution) in the absence of ADP (V₀), and in the presence of 0.1 mM ADP, 0.1 mM ADP + 20 mM creatine (Cr), and 1 mM ADP (V_max). The study was approved by the Ethics Committee of the Karolinska Institute.

Results
Following training, VO₂peak increased by 24% (p<0.01) and LT increased by 53% (p<0.01). V₀ and V_max increased by 35% (p<0.05) and 38% (p<0.05), respectively. The K_m for ADP increased from 0.12 ± 0.02 to 0.18 ± 0.01 mM (p<0.05), indicating decreased ADP sensitivity. In addition, the stimulation of respiration caused by creatine tended to increase (p= 0.057) following training. Respiration in the presence of ADP was decreased following ROS treatment and the decrease in respiratory rate did not differ between training states.

Conclusions
The increased V_max is in agreement with previously reported increases in mitochondrial density (Turner, 1997) and maximal ATP production rate (Wibom, 1992) following endurance training. The present study shows for the first time that short-term endurance training decreases ADP sensitivity. ADP is one of the major triggers of oxidative energy production and Cr/PCr can regulate the sensitivity of respiration to ADP. The combination of ADP sensitivity, regulation of ADP sensitivity by Cr/PCr, and the concentration of ADP and Cr/PCr constitute a sophisticated mode of control of oxidative phosphorylation previously observed in oxidative muscle (Kuznetsov 1996). The results also suggest that there is no up-regulation of ROS defenses following endurance training, which is consistent with the findings of Tiidus et al. (1996).