Linear relation between time constant of oxygen uptake kinetics, total creatine, and mitochondrial content in vitro

Brian Glancy, Thomas Barstow, Wayne T. Willis

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Following the onset of moderate aerobic exercise, the rate of oxygen consumption (Jo) rises monoexponentially toward the new steady state with a time constant (τ) in the vicinity of 30 s. The mechanisms underlying this delay have been studied over several decades. Meyer's electrical analog model proposed the concept that the τ is given by τ = R m·C, where Rm is mitochondrial resistance to energy transfer, and C is metabolic capacitance, determined primarily by the cellular total creatine pool (TCr = phosphocreatine + creatine). The purpose of this study was to evaluate in vitro the Jo kinetics of isolated rat skeletal muscle mitochondria at various levels of TCr and mitochondrial protein. Mitochondria were incubated in a medium containing 5.0 mM ATP, TCr pools of 0-1.5 mM, excess creatine kinase, and an ATP-splitting system of glucose + hexokinase (HK). Pyruvate and malate (1 mM each) were present as oxidative substrates. Jo was measured across time after HK was added to elicit one of two levels of Jo (40 and 60% of state 3). At TCr levels (in mM) of 0.1, 0.2, 0.3, 0.75, and 1.5, the corresponding τ values (s, means ± SE) were 22.2 ± 3.0, 36.3 ± 2.2, 65.7 ± 4.3, 168.1 ± 22.2, and 287.3 ± 25.9. Thus τ increased linearly with TCr (R2 = 0.916). Furthermore, the experimentally observed τ varied linearly and inversely with the mitochondrial protein added. These in vitro results consistently conform to the predictions of Meyer's electrical analog model.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume294
Issue number1
DOIs
StatePublished - Jan 2008

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Mitochondria
Hexokinase
Creatine
Mitochondrial Proteins
Adenosine Triphosphate
Muscle Mitochondrion
Oxygen
Kinetics
Phosphocreatine
Energy Transfer
Creatine Kinase
Pyruvic Acid
Oxygen Consumption
Energy transfer
Muscle
Rats
Skeletal Muscle
Capacitance
Exercise
Glucose

Keywords

  • Creatine kinase
  • Hexokinase
  • Mitochondrial resistance

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Linear relation between time constant of oxygen uptake kinetics, total creatine, and mitochondrial content in vitro. / Glancy, Brian; Barstow, Thomas; Willis, Wayne T.

In: American Journal of Physiology - Cell Physiology, Vol. 294, No. 1, 01.2008.

Research output: Contribution to journalArticle

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