title: Effects of the creatine analogue beta-guanidinopropionic acid on skeletal muscles of mice deficient in muscle creatine kinase.
abstract: To evaluate the effects of phosphocreatine (PCr) and creatine (Cr) depletion on skeletal muscles of mice deficient in muscle creatine kinase (M-CK), we have fed mutant mice a diet containing the creatine analogue beta-guanidinopropionic acid (beta GPA). After 8-10 weeks of feeding, accumulation of the creatine analogue in M-CK-deficient muscles was comparable to that observed in muscles of wild-type mice. Strikingly, and unlike wild types, mutants did not accumulate phosphorylated beta GPA, indicating that MM-CK is the only muscle CK isoform which can phosphorylate beta GPA. In M-CK-deficient muscles there was respective depletion of PCr, Cr and ATP levels to 31, 41 and 83% of normal. The average cross-sectional area of type 2B fibres in gastrocnemius muscles was very much reduced and was similar to type 1 and type 2A fibres which maintained their normal size. The maximal isometric twitch force developed by gastrocnemius-plantaris-soleus (GPS) muscle complexes of beta GPA-treated mutants was reduced by about 30%, but these muscles showed an increased fatigue resistance during 1 and 5 Hz contraction. Mitochondrial enzyme activities in the upper hind limb musculature of null mutants were 20-35% increased by the beta GPA diet. Altogether, these results provide evidence that certain functions of the creatine kinase/phosphocreatine (CK/PCr) system are not eliminated solely by the loss of M-CK.
authors.affiliation: Department of Cell Biology and Histology, Faculty of Medical Sciences, University of Nijmegen, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: van Deursen
authors.forename: P
authors.initials: P
authors.lastname: Jap
authors.forename: A
authors.initials: A
authors.lastname: Heerschap
authors.forename: H
authors.initials: H
authors.lastname: ter Laak
authors.forename: W
authors.initials: W
authors.lastname: Ruitenbeek
authors.forename: B
authors.initials: B
authors.lastname: Wieringa
mesh_terms: D000818:Animals; D003401:Creatine / Q000172:deficiency; D003402:Creatine Kinase / Q000172:deficiency*; D004734:Energy Metabolism; D006146:Guanidines / Q000494:pharmacology*; D051379:Mice; D008817:Mice, Mutant Strains; D009119:Muscle Contraction; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D010725:Phosphocreatine / Q000172:deficiency; D011422:Propionates / Q000494:pharmacology*
chemical_list: D006146:Guanidines; D011422:Propionates; D010725:Phosphocreatine; D003402:Creatine Kinase; D003401:Creatine; C005775:guanidinopropionic acid