Skeletal muscles of mice deficient in muscle creatine kinase lack burst activity

Deursen, Jan van; Heerschap, Arend; Oerlemans, Frank; Rultenbeek, Wim; Jap, P. H. K.; Laak, Henk ter; Wieringa, Bé

doi:10.1016/0092-8674(93)90510-w

Cited by 312 publications

(329 citation statements)

References 48 publications

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“…Previously, we had observed that M-CK absence is compensated by an adaptation in mitochondrial volume in type 2 (fast) fibers of the gastrocnemius-psoas-soleus (GPS) complex of M-CK [-/-] mice, but that the mitochondrial ultrastructure is otherwise fully normal [28,29]. To see whether other compensatory mechanisms were involved in ameliorating the complete loss of the Cr-PCr shuttle function in CK [-/-] animals we repeated the morphometric inspection and examined the fiber ultrastructure of diaphragm, heart, intercostal, gastrocnemius and soleus muscles.…”

Section: Consequences For Mitochondria and Er Membranesmentioning

confidence: 99%

“…Sample preparation, pre-and post-fixation and Epon embedding was exactly as described [28]. Ultrathin sections, double contrasted with uranyl acetate, were examined in a Philips electron microscope EM 301 or a JEOL TEM 1010.…”

Section: Light Microscopical Ultrastructural and Biochemical Fiber Tmentioning

confidence: 99%

“…Our group has generated mice completely deficient in M-CK subunits and mice expressing reduced levels of M-CK, by gene targeting. The biological consequences of these mutations have been characterised [28,29]. Likewise, animals lacking either the ubiquitous mitochondrial CK subform (UbCKmit), or the sarcomeric mitochondrial CK (ScCKmit) isoenzyme, with suprisingly little phenotypic effects, have been generated [30,31].…”

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confidence: 99%

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Cytoarchitectural and metabolic adaptations in muscles with mitochondrial and cytosolic creatine kinase deficiencies

Steeghs¹,

Oerlemans²,

Haan³

et al. 1998

Bioenergetics of the Cell: Quantitative Aspects

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Section: Consequences For Mitochondria and Er Membranesmentioning

confidence: 99%

Section: Light Microscopical Ultrastructural and Biochemical Fiber Tmentioning

confidence: 99%

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confidence: 99%

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Cytoarchitectural and metabolic adaptations in muscles with mitochondrial and cytosolic creatine kinase deficiencies

Steeghs¹,

Oerlemans²,

Haan³

et al. 1998

Bioenergetics of the Cell: Quantitative Aspects

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“…Inhibition of CK in muscle using substrate analogues (30 -32) or gene knockout of MM-CK and mitochondrial CK (33)(34)(35)(36) has been shown to lead to large contractile abnormalities and alterations in muscle cell size and alterations in mitochondrial and glycolytic capacity. These results clearly demonstrate the important role of CK in normal muscle function but do not specifically address whether the CK isoform expression that is localized to myofibrils plays an important role in contractile function.…”

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confidence: 99%

Functional Equivalence of Creatine Kinase Isoforms in Mouse Skeletal Muscle

Roman¹,

Wieringa²,

Koretsky³

1997

Journal of Biological Chemistry

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Creatine kinase (CK) is a highly conserved enzyme abundant in skeletal muscle that has a key role in high energy phosphate metabolism. The localization of the muscle isoenzyme of CK (MM-CK) to the M line and the sarcoplasmic reticulum of myofibrils has been suggested to be important for proper force development in skeletal muscle. The importance of this subcellular compartmentation has not been directly tested in vivo. To test the role of myofibrilar localization of CK, the consequences of a complete CK isoform switch from MM-CK to the brain (BB-CK) isoform, which does not localize to the M line, was studied in transgenic mouse skeletal muscle. In MM-CK knockout mice there are large contractile defects. When MM-CK was replaced by BB-CK, the aberrant contractile phenotypes seen in MM-CK knockout mice were returned to normal despite the lack of myofibrillar localization. These results indicate that CK compartmentation to the myofibril of skeletal muscle is not essential for contractile function and that there is functional equivalence of creatine kinase isoforms in supporting cellular energy metabolism.

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“…Those levels are constant for the next 10-15 min and then they slowly increase [6,7]. The animals with suppressed Cr-CrP shuttle lacked burst muscle activity for = 1 min but afterwards showed a relatively increased muscle endurance [7,8,11,28]. It is clear that the kinetic behavior of the designed model satisfactory represents the experimental data and testifies to the validity of the model (at least for the 2 minutes of simulations).…”

Section: Discussionmentioning

confidence: 62%

Creatine-creatine phosphate shuttle modeled as two-compartment system at different levels of creatine kinase activity

Fedosov

1994

Biochimica et Biophysica Acta (BBA) - Protein Structure and Mol

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In order to characterize ADP-ATP and creatine-creatine phosphate (Cr-CrP) shuttles a minimal mathematical model with two compartments and cyclic turnover of matter was designed. The 'mitochondrial' compartment contained 'ATP-synthase' and 'mitochondrial ereatine kinase' (mitCK). The 'cytoplasmic' compartment consisted of 'ATPase', 'cytoplasmic creatine kinase' (cytCK) and an 'ADP-binding structure'. The exchange of metabolites between these compartments was limited. Different levels of cytCK and mitCK expression as welt as different exchange rate constants between the compartments were assigned to obtain several different modes. Every steady state obtained in the presence of low ATPase activity ('resting' conditions) was then disturbed by a steep activation of ATPase ('muscle performance') and afterwards the transition to a new steady state was followed in time. The ATP-buffering capacity of the system initially acquired by cytCK expression significantly increased after additional mitCK supplement. Nevertheless, even the complete Cr-CrP shuttle failed to maintain a high [ATP]/[ADP] ratio during long term 'muscle performance' due to the rate limiting CK-transphosphorylation in the mitochondria. The facilitated diffusion of Cr and CrP was not critical, and the model worked with the same efficiency even at equal permeabilities for nucleotides and guanidines. Under 'resting conditions' the main flux of matter went through the Cr-CrP shuttle, resulting in 'pumping' of CrP. This ensured a 40 s delay in the [ATP] decrease at 'work'. The partial systems without mitCK were not as effective, and this delay was 0-10 s. However, the ADP-ATP shuttle was of more importance at the steady state achieved under ' working' conditions.

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Skeletal muscles of mice deficient in muscle creatine kinase lack burst activity

Cited by 312 publications

References 48 publications

Cytoarchitectural and metabolic adaptations in muscles with mitochondrial and cytosolic creatine kinase deficiencies

Cytoarchitectural and metabolic adaptations in muscles with mitochondrial and cytosolic creatine kinase deficiencies

Functional Equivalence of Creatine Kinase Isoforms in Mouse Skeletal Muscle

Creatine-creatine phosphate shuttle modeled as two-compartment system at different levels of creatine kinase activity

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