title: Role of pyruvate dehydrogenase kinase 4 in regulating PDH activation during acute muscle contraction.
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.
authors.affiliation: Department of Kinesiology, Brock University, ON N1G 2W1, Canada.
authors.forename: Eric A F
authors.initials: EA
authors.lastname: Herbst
authors.forename: Emily C E
authors.initials: EC
authors.lastname: Dunford
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harris
authors.forename: Rene
authors.initials: R
authors.lastname: Vandenboom
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Leblanc
authors.forename: Brian D
authors.initials: BD
authors.lastname: Roy
authors.forename: Nam Ho
authors.initials: NH
authors.lastname: Jeoung
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Peters
mesh_terms: D000818:Animals; D050260:Carbohydrate Metabolism; D004558:Electric Stimulation; D004789:Enzyme Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000201:enzymology*; D010084:Oxidation-Reduction; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D013997:Time Factors
chemical_list: C000631433:Pdk1 protein, mouse; C000631439:Pdk4 protein, mouse; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011768:Pyruvate Dehydrogenase Complex; D017346:Protein Serine-Threonine Kinases