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 Citations (Scopus)

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 rype 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
JournalBiochimica et Biophysica Acta - Bioenergetics
Volume1185
Issue number3
DOIs
StatePublished - 1994
Externally publishedYes

Fingerprint

MM Form Creatine Kinase
Creatine
Muscle
Skeletal Muscle
Phosphocreatine
Muscles
Diet
Nutrition
Creatine Kinase
Upper Extremity
Fatigue
Protein Isoforms
Adenosine Triphosphate
guanidinopropionic acid
Fibers
Enzyme activity
Enzymes
Fatigue of materials

Keywords

  • β-guanidinopropionic acid
  • CK/PCr system
  • creatine kinase deficiency
  • M-CK-deficient mice
  • muscle
  • phosphocreatine
  • skeletal muscle bioenergetics

ASJC Scopus subject areas

  • Biophysics

Cite this

Effects of the creatine analogue β-guanidinopropionic acid on skeletal muscles of mice deficient in muscle creatine kinase. / Van Deursen, Jan; Jap, Paul; Heerschap, Arend; Ter Laak, Henk; Ruitenbeek, Wim; Wieringa, Bé.

In: Biochimica et Biophysica Acta - Bioenergetics, Vol. 1185, No. 3, 1994, p. 327-335.

Research output: Contribution to journalArticle

Van Deursen, Jan ; Jap, Paul ; Heerschap, Arend ; Ter Laak, Henk ; Ruitenbeek, Wim ; Wieringa, Bé. / Effects of the creatine analogue β-guanidinopropionic acid on skeletal muscles of mice deficient in muscle creatine kinase. In: Biochimica et Biophysica Acta - Bioenergetics. 1994 ; Vol. 1185, No. 3. pp. 327-335.
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