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Presence of (phospho)creatine in developing and adult skeletal muscle of mice without mitochondrial and cytosolic muscle creatine kinase isoforms

in 't Zandt, H J A LU ; de Groof, A J C; Renema, W K J; Oerlemans, F T J J; Klomp, D W J; Wieringa, B and Heerschap, Arend (2003) In Journal of Physiology 548(Pt 3). p.58-847
Abstract

We assessed the relationship between phosphocreatine (PCr) and creatine (Cr) content and creatine kinase (CK) activity in skeletal muscle of mice. The PCr and total Cr (tCr) concentrations, as well as CK activity, in hindlimb muscles of mice, with or without the cytosolic and mitochondrial isoforms of muscle creatine kinase (wild-type or CK--/-- mice), were determined by in vivo magnetic resonance (MR) spectroscopy and by biochemical means during postnatal growth and adulthood. In wild-type muscle the [tCr], PCr/ATP ratio and CK activity increased rapidly in the first 4-7 weeks. Remarkably, CK--/-- mice showed a similar increase in the PCr/ATP ratio during the first month in the presence of only minor brain-type BB-CK activity. Uptake... (More)

We assessed the relationship between phosphocreatine (PCr) and creatine (Cr) content and creatine kinase (CK) activity in skeletal muscle of mice. The PCr and total Cr (tCr) concentrations, as well as CK activity, in hindlimb muscles of mice, with or without the cytosolic and mitochondrial isoforms of muscle creatine kinase (wild-type or CK--/-- mice), were determined by in vivo magnetic resonance (MR) spectroscopy and by biochemical means during postnatal growth and adulthood. In wild-type muscle the [tCr], PCr/ATP ratio and CK activity increased rapidly in the first 4-7 weeks. Remarkably, CK--/-- mice showed a similar increase in the PCr/ATP ratio during the first month in the presence of only minor brain-type BB-CK activity. Uptake of Cr in muscle was seemingly unrelated to CK activity as tCr increased in the same way in the muscles of both mouse types. At older ages the PCr/ATP ratio decreased in CK--/-- muscles, in contrast to wild-type where it still slowly increased, whereas [tCr] was similar for muscle of both mouse types. Using a new in vivo MR approach with application of [4-13C]Cr, a lower PCr/tCr ratio was also observed in CK--/-- muscle. From these data it follows that in vivo global ATP levels at rest are similar in the presence or absence of CK. Although Cr could still be converted to PCr in mature CK--/-- muscle, the immediate availability of PCr decreased, and PCr became partly inconvertible at older ages. Apparently, catalysis of the CK reaction by BB-CK, although significant in muscles of newborn mice, gradually declines to very low levels in adulthood. Part or all of this BB-CK may arise from satellite cells fusing with myotubes, a process that is most active during the first months of life. Finally, our observation that the MR and chemical assessment of muscle [tCr] and PCr/tCr ratio were similar for all mice does not support the existence of a significant MR-invisible or immobile pool of Cr, with a role for CK in this phenomenon.

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publishing date
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Contribution to journal
publication status
published
keywords
Adenylate Kinase, Aging, Animals, Creatine, Creatine Kinase, Creatine Kinase, MM Form, Cytosol, Hindlimb, Isoenzymes, Kinetics, Magnetic Resonance Imaging, Mice, Mice, Knockout, Mitochondria, Muscle, Muscle, Skeletal, Phosphocreatine, Phosphorylation, Journal Article, Research Support, Non-U.S. Gov't
in
Journal of Physiology
volume
548
issue
Pt 3
pages
12 pages
publisher
The Physiological Society
external identifiers
  • scopus:0037648681
ISSN
0022-3751
DOI
10.1113/jphysiol.2002.034538
language
English
LU publication?
no
id
386fb358-c335-412f-81f2-f74ee6abe908
date added to LUP
2017-03-06 17:11:04
date last changed
2017-05-18 14:33:28
@article{386fb358-c335-412f-81f2-f74ee6abe908,
  abstract     = {<p>We assessed the relationship between phosphocreatine (PCr) and creatine (Cr) content and creatine kinase (CK) activity in skeletal muscle of mice. The PCr and total Cr (tCr) concentrations, as well as CK activity, in hindlimb muscles of mice, with or without the cytosolic and mitochondrial isoforms of muscle creatine kinase (wild-type or CK--/-- mice), were determined by in vivo magnetic resonance (MR) spectroscopy and by biochemical means during postnatal growth and adulthood. In wild-type muscle the [tCr], PCr/ATP ratio and CK activity increased rapidly in the first 4-7 weeks. Remarkably, CK--/-- mice showed a similar increase in the PCr/ATP ratio during the first month in the presence of only minor brain-type BB-CK activity. Uptake of Cr in muscle was seemingly unrelated to CK activity as tCr increased in the same way in the muscles of both mouse types. At older ages the PCr/ATP ratio decreased in CK--/-- muscles, in contrast to wild-type where it still slowly increased, whereas [tCr] was similar for muscle of both mouse types. Using a new in vivo MR approach with application of [4-13C]Cr, a lower PCr/tCr ratio was also observed in CK--/-- muscle. From these data it follows that in vivo global ATP levels at rest are similar in the presence or absence of CK. Although Cr could still be converted to PCr in mature CK--/-- muscle, the immediate availability of PCr decreased, and PCr became partly inconvertible at older ages. Apparently, catalysis of the CK reaction by BB-CK, although significant in muscles of newborn mice, gradually declines to very low levels in adulthood. Part or all of this BB-CK may arise from satellite cells fusing with myotubes, a process that is most active during the first months of life. Finally, our observation that the MR and chemical assessment of muscle [tCr] and PCr/tCr ratio were similar for all mice does not support the existence of a significant MR-invisible or immobile pool of Cr, with a role for CK in this phenomenon.</p>},
  author       = {in 't Zandt, H J A and de Groof, A J C and Renema, W K J and Oerlemans, F T J J and Klomp, D W J and Wieringa, B and Heerschap, Arend},
  issn         = {0022-3751},
  keyword      = {Adenylate Kinase,Aging,Animals,Creatine,Creatine Kinase,Creatine Kinase, MM Form,Cytosol,Hindlimb,Isoenzymes,Kinetics,Magnetic Resonance Imaging,Mice,Mice, Knockout,Mitochondria, Muscle,Muscle, Skeletal,Phosphocreatine,Phosphorylation,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {05},
  number       = {Pt 3},
  pages        = {58--847},
  publisher    = {The Physiological Society},
  series       = {Journal of Physiology},
  title        = {Presence of (phospho)creatine in developing and adult skeletal muscle of mice without mitochondrial and cytosolic muscle creatine kinase isoforms},
  url          = {http://dx.doi.org/10.1113/jphysiol.2002.034538},
  volume       = {548},
  year         = {2003},
}