Skeletal muscle function and structure after depletion of creatine.
Experiments were conducted to determine if normal skeletal muscle function and structure are dependent upon their ability to store large quantities of metabolic energy in the form of N-phosphorylcreatine. Muscle levels of creatine and N-phosphorylcreatine were reduced by feeding young male rats diets containing 1 per cent beta-guanidinopropionic acid (beta-GPA). Muscle function was evaluated by monitoring performance during a 4-week, short duration, high intensity exercise program in a control running wheel. Structural effects were determined by histochemistry, morphometric analysis, and routine histologic procedures using light microscopy. Evidence of abnormal creatine metabolism of rats fed beta-GPA included: excessive creatinuria, reduction in urine creatinine, reduced levels of muscle and brain creatine, and a reduced activity of muscle creatine kinase. In separate experiments, beta-GPA inhibited the reaction of creatine with creatine kinase in vitro. When muscle function was evaluated by running, the percentage of expected revolutions for the group of rats fed beta-GPA was below the expected normal values. The white (type II) fibers from the gastrocnemius of exercised rats fed beta-GPA were smaller than fibers from the same muscle areas of rats fed normal diets. The histochemical characteristics of red (type I) and white fibers of all rats tested were within normal limits. It is concluded that feeding beta-GPA will result in structural and functional changes in skeletal muscles of exercised young male rats. These changes are believed to result from the ability of beta-GPA to block creatine entry into muscle and thereby prevent muscle from accumulating and maintaining its normal complement of creatine and N-phosphorylcreatine.
D000818:Animals; D001921:Brain / Q000378:metabolism; D003401:Creatine / Q000378:metabolism* / Q000502:physiology / Q000652:urine; D003402:Creatine Kinase / Q000378:metabolism; D003404:Creatinine / Q000652:urine; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D009132:Muscles / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D011422:Propionates / Q000494:pharmacology; D051381:Rats
D006146:Guanidines; D011422:Propionates; D003404:Creatinine; D003402:Creatine Kinase; D003401:Creatine