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 journalArticle

200 Citations (Scopus)

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 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
JournalCell
Volume89
Issue number1
StatePublished - Apr 4 1997
Externally publishedYes

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Mitochondrial Form Creatine Kinase
Phosphocreatine
Creatine Kinase
Muscle
Muscles
Mitochondrial Size
Skeletal Muscle Fibers
Sarcoplasmic Reticulum
Muscle Contraction
Electrolytes
Gene encoding
Skeletal Muscle
Adenosine Triphosphate
Relaxation time
Mutation
Membranes
Fluxes
Genes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Steeghs, K., Benders, A., Oerlemans, F., De Haan, A., Heerschap, A., Ruitenbeek, W., ... Wieringa, B. (1997). Altered Ca2+ responses in muscles with combined mitochondrial and cytosolic creatine kinase deficiencies. Cell, 89(1), 93-103.

Altered Ca2+ responses in muscles with combined mitochondrial and cytosolic creatine kinase deficiencies. / Steeghs, Karen; Benders, Ad; Oerlemans, Frank; De Haan, Arnold; Heerschap, Arend; Ruitenbeek, Wim; Jost, Carolina; Van Deursen, Jan; Perryman, Benjamin; Pette, Dirk; Brückwilder, Marloes; Koudijs, Jolande; Paul, Jap; Veerkamp, Jacques; Wieringa, Bé.

In: Cell, Vol. 89, No. 1, 04.04.1997, p. 93-103.

Research output: Contribution to journalArticle

Steeghs, K, Benders, A, Oerlemans, F, De Haan, A, Heerschap, A, Ruitenbeek, W, Jost, C, Van Deursen, J, Perryman, B, Pette, D, Brückwilder, M, Koudijs, J, Paul, J, Veerkamp, J & Wieringa, B 1997, 'Altered Ca2+ responses in muscles with combined mitochondrial and cytosolic creatine kinase deficiencies', Cell, vol. 89, no. 1, pp. 93-103.
Steeghs K, Benders A, Oerlemans F, De Haan A, Heerschap A, Ruitenbeek W et al. Altered Ca2+ responses in muscles with combined mitochondrial and cytosolic creatine kinase deficiencies. Cell. 1997 Apr 4;89(1):93-103.
Steeghs, Karen ; Benders, Ad ; Oerlemans, Frank ; De Haan, Arnold ; Heerschap, Arend ; Ruitenbeek, Wim ; Jost, Carolina ; Van Deursen, Jan ; Perryman, Benjamin ; Pette, Dirk ; Brückwilder, Marloes ; Koudijs, Jolande ; Paul, Jap ; Veerkamp, Jacques ; Wieringa, Bé. / Altered Ca2+ responses in muscles with combined mitochondrial and cytosolic creatine kinase deficiencies. In: Cell. 1997 ; Vol. 89, No. 1. pp. 93-103.
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