Physical activity changes the regulation of mitochondrial respiration in human skeletal muscle

Abstract

This study explores the importance of creatine kinase (CK) in the regulation of muscle mitochondrial respiration in human subjects depending on their level of physical activity. Volunteers were classified as sedentary, active or athletic according to the total activity index as determined by the Baecke questionnaire in combination with maximal oxygen uptake values (peak V̇O2, expressed in ml min−1 kg−1). All volunteers underwent a cyclo‐ergometric incremental exercise test to estimate their peak V̇O2 and V̇O2 at the ventilatory threshold (VT). Muscle biopsy samples were taken from the vastus lateralis and mitochondrial respiration was evaluated in an oxygraph cell on saponin permeabilised muscle fibres in the absence (V̇0) or in the presence (V̇max) of saturating [ADP]. While V̇0 was similar, V̇max differed among groups (sedentary, 3.7 ± 0.3, active, 5.9 ± 0.9 and athletic, 7.9 ± 0.5 μmol O 2 min−1 (g dry weight)−1). V̇max was correlated with peak V̇O2 (P < 0.01, r= 0.63) and with V̇T (P < 0.01, r= 0.57). There was a significantly greater degree of coupling between oxidation and phosphorylation (V̇max/V̇0) in the athletic individuals. The mitochondrial Km for ADP was significantly higher in athletic subjects (P < 0.01). Mitochondrial CK (mi‐CK) activation by addition of creatine induced a marked decrease in Km in athletic individuals only, indicative of an efficient coupling of mi‐CK to ADP rephosphorylation in the athletic subjects only. It is suggested that increasing aerobic performance requires an enhancement of both muscle oxidative capacity and mechanisms of respiratory control, attesting to the importance of temporal co‐ordination of energy fluxes by CK for higher efficacy.