title: Altered Ca2+ responses in muscles with combined mitochondrial and cytosolic creatine kinase deficiencies.
abstract: We have blocked creatine kinase (CK)-mediated phosphocreatine (PCr) -->/<-- ATP transphosphorylation in skeletal muscle by combining targeted mutations in the genes encoding mitochondrial and cytosolic CK in mice. Contrary to expectation, the PCr level was only marginally affected, but the compound was rendered metabolically inert. Mutant muscles in vivo showed significantly impaired tetanic force output, increased relaxation times, altered mitochondrial volume and location, and conspicuous tubular aggregates of sarcoplasmic reticulum membranes, as seen in myopathies with electrolyte disturbances. In depolarized myotubes cultured in vitro, CK absence influenced both the release and sequestration of Ca2+. Our data point to a direct link between the CK-PCr system and Ca2+-flux regulation during the excitation and relaxation phases of muscle contraction.
authors.affiliation: Department of Cell Biology and Histology, Faculty of Medical Sciences, University of Nijmegen, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Steeghs
authors.forename: A
authors.initials: A
authors.lastname: Benders
authors.forename: F
authors.initials: F
authors.lastname: Oerlemans
authors.forename: A
authors.initials: A
authors.lastname: de Haan
authors.forename: A
authors.initials: A
authors.lastname: Heerschap
authors.forename: W
authors.initials: W
authors.lastname: Ruitenbeek
authors.forename: C
authors.initials: C
authors.lastname: Jost
authors.forename: J
authors.initials: J
authors.lastname: van Deursen
authors.forename: B
authors.initials: B
authors.lastname: Perryman
authors.forename: D
authors.initials: D
authors.lastname: Pette
authors.forename: M
authors.initials: M
authors.lastname: Brückwilder
authors.forename: J
authors.initials: J
authors.lastname: Koudijs
authors.forename: P
authors.initials: P
authors.lastname: Jap
authors.forename: J
authors.initials: J
authors.lastname: Veerkamp
authors.forename: B
authors.initials: B
authors.lastname: Wieringa
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured / Q000201:enzymology; D003402:Creatine Kinase / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology*; D004594:Electrophysiology; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D006868:Hydrolysis; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D008928:Mitochondria / Q000201:enzymology*; D018485:Muscle Fibers, Skeletal / Q000201:enzymology; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology*; D016296:Mutagenesis / Q000502:physiology; D010641:Phenotype; D010725:Phosphocreatine / Q000378:metabolism
chemical_list: D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D002118:Calcium