Faster O₂ uptake kinetics in canine skeletal muscle in situ after acute creatine kinase inhibition

J Physiol. 2011 Jan 1;589(Pt 1):221-33. doi: 10.1113/jphysiol.2010.195164. Epub 2010 Nov 8.


Creatine kinase (CK) plays a key role both in energy provision and in signal transduction for the increase in skeletal muscle O2 uptake () at exercise onset. The effects of acute CK inhibition by iodoacetamide (IA; 5 mm) on kinetics were studied in isolated canine gastrocnemius muscles in situ (n = 6) during transitions from rest to 3 min of electrically stimulated contractions eliciting ∼70% of muscle peak , and were compared to control (Ctrl) conditions. In both IA and Ctrl muscles were pump-perfused with constantly elevated blood flows. Arterial and venous [O2] were determined at rest and every 5-7 s during contractions. was calculated by Fick's principle. Muscle biopsies were obtained at rest and after ∼3 min of contractions. Muscle force was measured continuously. There was no fatigue in Ctrl (final force/initial force (fatigue index, FI) = 0.97 ± 0.06 (x ± s.d.)), whereas in IA force was significantly lower during the first contractions, slightly recovered at 15-20 s and then decreased (FI 0.67 ± 0.17). [Phosphocreatine] was not different in the two conditions at rest, and decreased during contractions in Ctrl, but not in IA. at 3 min was lower in IA (4.7 ± 2.9 ml 100 g-1 min-1) vs. Ctrl (16.6 ± 2.5 ml 100 g-1 min-1). The time constant (τ) of kinetics was faster in IA (8.1 ± 4.8 s) vs. Ctrl (16.6 ± 2.6 s). A second control condition (Ctrl-Mod) was produced by modelling a response that accounted for the 'non-square' force profile in IA, which by itself could have influenced kinetics. However, τ in IA was faster than in Ctrl-Mod (13.8 ± 2.8 s). The faster kinetics due to IA suggest that in mammalian skeletal muscle in situ, following contractions onset, temporal energy buffering by CK slows the kinetics of signal transduction for the activation of oxidative phosphorylation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biopsy
  • Creatine Kinase, MM Form / antagonists & inhibitors*
  • Creatine Kinase, MM Form / metabolism
  • Dogs
  • Electric Stimulation
  • Enzyme Inhibitors / pharmacology*
  • Female
  • In Vitro Techniques
  • Iodoacetamide / pharmacology*
  • Kinetics
  • Male
  • Models, Biological
  • Muscle Contraction*
  • Muscle Strength
  • Muscle, Skeletal / blood supply
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / innervation
  • Oxidative Phosphorylation
  • Oxygen / metabolism*
  • Oxygen Consumption / drug effects*
  • Perfusion
  • Phosphocreatine / metabolism
  • Regional Blood Flow
  • Up-Regulation


  • Enzyme Inhibitors
  • Phosphocreatine
  • Creatine Kinase, MM Form
  • Oxygen
  • Iodoacetamide