Effects of the creatine analogue β-guanidinopropionic acid on skeletal muscles of mice deficient in muscle creatine kinase

Jan van Deursen, Paul Jap, Arend Heerschap, Henk ter Laak, Wim Ruitenbeek, Bé Wieringa

Research output: Contribution to journalArticle

33 Scopus citations

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 β-guanidinopropionic acid (βGPA). 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 βGPA, indicating that MM-CK is the only muscle CK isoform which can phosphorylate βGPA. 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 βGPA-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 βGPA 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.

Original languageEnglish (US)
Pages (from-to)327-335
Number of pages9
JournalBBA - Bioenergetics
Volume1185
Issue number3
DOIs
StatePublished - May 18 1994

Keywords

  • (M-CK-deficient mice)
  • CK/PCr system
  • Creatine kinase deficiency
  • Muscle
  • Phosphocreation
  • Skeletal muscle bioenergetics
  • β-Guanidinopropionic acid

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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