Contractile economy and aerobic recovery metabolism in skeletal muscle adapted to creatine depletion

Abstract

Mice were treated for 7-12 wk with the creatine analogue beta-guanidinopropionic acid (beta-GPA). Treatment reduced total creatine to approximately 5% of control values in soleus (SOL) and extensor digitorum longus (EDL) muscles. In both muscles from treated mice, phosphorylated beta-GPA accumulated and resting [ATP] decreased by approximately 50%. Relative to controls, cytochrome oxidase and citrate synthase activities increased significantly in EDL from treated mice, but not in SOL; creatine kinase activity decreased significantly in SOL, but not in EDL. Measurements of poststimulation energy metabolism show that the energy cost to maintain tension in SOL and EDL from treated mice was approximately 50% of that in control muscle. Relative to controls, first-order rate constants of poststimulation O2 demand were 2- and 3.6-fold greater in SOL and EDL, respectively, from treated mice. Increased economy of SOL and EDL from treated mice is consistent with previously reported changes in myosin isoenzymes. Increases in rate constants of O2 utilization in creatine-depleted muscle are inconsistent with the hypothesis that cytoplasmic or mitochondrial creatine kinase is rate limiting for cellular respiration.