Altered Ca2+ responses in muscles with combined mitochondrial and cytosolic creatine kinase deficiencies

Karen Steeghs, Ad Benders, Frank Oerlemans, Arnold De Haan, Arend Heerschap, Wim Ruitenbeek, Carolina Jost, Jan Van Deursen, Benjamin Perryman, Dirk Pette, Marloes Brückwilder, Jolande Koudijs, Jap Paul, Jacques Veerkamp, Bé Wieringa

Research output: Contribution to journalArticlepeer-review

206 Scopus citations


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 myopsthies 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.

Original languageEnglish (US)
Pages (from-to)93-103
Number of pages11
Issue number1
StatePublished - Apr 4 1997

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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