Role of pyruvate dehydrogenase kinase 4 in regulating PDH activation during acute muscle contraction

Eric A F Herbst, Emily C E Dunford, Robert Harris, Rene Vandenboom, Paul J. LeBlanc, Brian D. Roy, Nam Ho Jeoung, Sandra J. Peters

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The oxidation of carbohydrates in mammals is regulated by the pyruvate dehydrogenase (PDH) complex, which is covalently regulated by four PDH kinases (PDK1-4) and two PDH phosphatases (PDP1-2) unique to the PDH complex. To investigate the role that PDK4 plays in regulating PDH activation (PDHa) during muscle contraction, mouse extensor digitorum muscle was removed from wild type (WT) and PDK4-knockout (PDK4-KO) mice after a 24 h fast and stimulated for 3 min either at 10 Hz (low-intensity contraction), 40 Hz (moderate-intensity contraction), or allowed to rest. Force was recorded and muscle PDHa activity and metabolite concentrations were measured. PDHa activity was ~2.5-fold higher at rest in PDK4-KO mice than WT mice (P = 0.009) and ~2-fold higher in PDK4-KO mice at both 10 Hz (P < 0.001) and 40 Hz (P < 0.001). Force relative to muscle weight was similar at 10 Hz, but was 5.8 ± 0.7 mN·g -1 in PDK4-KO mice and 3.5 ± 0.7 mN·g -1 in WT mice at 40 Hz (P < 0.001), with a similar rate of fatigue in both genotypes. From these results it was concluded that PDK4 plays a role in reducing PDHa activity during low to moderate-intensity muscle stimulation, and that absence of PDK4 and the subsequent changes in carbohydrate utilization may alter force production.

Original languageEnglish
Pages (from-to)48-52
Number of pages5
JournalApplied Physiology, Nutrition and Metabolism
Volume37
Issue number1
DOIs
StatePublished - Feb 2012

Fingerprint

Muscle Contraction
Pyruvic Acid
Knockout Mice
Oxidoreductases
Pyruvate Dehydrogenase Complex
Muscles
Pyruvate Dehydrogenase (Lipoamide)-Phosphatase
Carbohydrates
Fatigue
Mammals
Genotype
Weights and Measures
pyruvate dehydrogenase kinase 4

Keywords

  • Muscle contraction
  • PDH regulation
  • PDK4

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics
  • Physiology (medical)

Cite this

Herbst, E. A. F., Dunford, E. C. E., Harris, R., Vandenboom, R., LeBlanc, P. J., Roy, B. D., ... Peters, S. J. (2012). Role of pyruvate dehydrogenase kinase 4 in regulating PDH activation during acute muscle contraction. Applied Physiology, Nutrition and Metabolism, 37(1), 48-52. https://doi.org/10.1139/H11-136

Role of pyruvate dehydrogenase kinase 4 in regulating PDH activation during acute muscle contraction. / Herbst, Eric A F; Dunford, Emily C E; Harris, Robert; Vandenboom, Rene; LeBlanc, Paul J.; Roy, Brian D.; Jeoung, Nam Ho; Peters, Sandra J.

In: Applied Physiology, Nutrition and Metabolism, Vol. 37, No. 1, 02.2012, p. 48-52.

Research output: Contribution to journalArticle

Herbst, EAF, Dunford, ECE, Harris, R, Vandenboom, R, LeBlanc, PJ, Roy, BD, Jeoung, NH & Peters, SJ 2012, 'Role of pyruvate dehydrogenase kinase 4 in regulating PDH activation during acute muscle contraction', Applied Physiology, Nutrition and Metabolism, vol. 37, no. 1, pp. 48-52. https://doi.org/10.1139/H11-136
Herbst, Eric A F ; Dunford, Emily C E ; Harris, Robert ; Vandenboom, Rene ; LeBlanc, Paul J. ; Roy, Brian D. ; Jeoung, Nam Ho ; Peters, Sandra J. / Role of pyruvate dehydrogenase kinase 4 in regulating PDH activation during acute muscle contraction. In: Applied Physiology, Nutrition and Metabolism. 2012 ; Vol. 37, No. 1. pp. 48-52.
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