TY - JOUR
T1 - Effects of the creatine analogue β-guanidinopropionic acid on skeletal muscles of mice deficient in muscle creatine kinase
AU - van Deursen, Jan
AU - Jap, Paul
AU - Heerschap, Arend
AU - ter Laak, Henk
AU - Ruitenbeek, Wim
AU - Wieringa, Bé
N1 - Funding Information:
The authors wish to thank Mietske Wijers-Rouw, Theo van Lith, Antoon Janssen andH enny Kuppen for their technical assistance,H ans Degens and Rob Binkhorst (Depanmcoot f Physiologyf)o r help in muscle force measurementsJa, n(he van Ree and David lies for critic,:l!yr eadingthe manuscripta, nd our cot-leagueso f the Central Animal Facility for help and advice. This work was supportedb y a program grant from the Dutch scienceo rgan(sat(onN, WO-GB-MW, and carried out at the NMR facilities of the Department of Biophysical Chemistry, Universityo f Nij-megenw, ith the support of NWO-SON.
PY - 1994/5/18
Y1 - 1994/5/18
N2 - 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.
AB - 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.
KW - (M-CK-deficient mice)
KW - CK/PCr system
KW - Creatine kinase deficiency
KW - Muscle
KW - Phosphocreation
KW - Skeletal muscle bioenergetics
KW - β-Guanidinopropionic acid
UR - http://www.scopus.com/inward/record.url?scp=0028290790&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028290790&partnerID=8YFLogxK
U2 - 10.1016/0005-2728(94)90248-8
DO - 10.1016/0005-2728(94)90248-8
M3 - Article
C2 - 8180237
AN - SCOPUS:0028290790
SN - 0005-2728
VL - 1185
SP - 327
EP - 335
JO - BBA - Bioenergetics
JF - BBA - Bioenergetics
IS - 3
ER -