Diaphragm and cardiac mitochondrial creatine kinases are impaired in sepsis

Leigh A. Callahan, Gerald S. Supinski

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Previous studies indicate that ATP formation by the electron transport chain is impaired in sepsis. However, it is not known whether sepsis affects the mitochondrial ATP transport system. We hypothesized that sepsis inactivates the mitochondrial creatine kinase (MtCK)-high energy phosphate transport system. To examine this issue, we assessed the effects of endotoxin administration on mitochondrial membrane-bound creatine kinase, an important trans-mitochondrial ATP transport system. Diaphragms and hearts were isolated from control (n = 12) and endotoxin-treated (8 mg·kg-1·day-1; n = 13) rats after pentobarbital anesthesia. We isolated mitochondria using techniques that allow evaluation of the functional coupling of mitochondrial creatine kinase MtCK activity to oxidative phosphorylation. MtCK functional activity was established by 1) determining ATP/creatine-stimulated oxygen consumption and 2) assessing total creatine kinase activity in mitochondria using an enzyme-linked assay. We examined MtCK protein content using Western blots. Endotoxin markedly reduced diaphragm and cardiac MtCK activity, as determined both by ATP/creatine-stimulated oxygen consumption and by the enzyme-linked assay (e.g., ATP/creatine-stimulated mitochondrial respiration was 173.8 ± 7.3, 60.5 ± 9.3, 210.7 ± 18.9, was 67.9 ± 7.3 natoms O·min-1·mg-1 in diaphragm control, diaphragm septic, cardiac control, and cardiac septic samples, respectively; P < 0.001 for each tissue comparison). Endotoxin also reduced diaphragm and cardiac MtCK protein levels (e.g., protein levels declined by 39.5% in diaphragm mitochondria and by 44.2% in cardiac mitochondria; P < 0.001 and P = 0.009, respectively, comparing sepsis to control conditions). Our data indicate that endotoxin markedly impairs the MtCK-ATP transporter system; this phenomenon may have significant effects on diaphragm and cardiac function.

Original languageEnglish
Pages (from-to)44-53
Number of pages10
JournalJournal of Applied Physiology
Issue number1
StatePublished - Jan 2007


  • ATP/creatine stimulated respiration
  • Endotoxin
  • Heart
  • Mitochondrial creatine kinase activity
  • Respiratory muscles

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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