Role of pyruvate dehydrogenase kinase 4 in regulating PDH activation during acute muscle contraction |
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Authors: | Herbst Eric A F Dunford Emily C E Harris Robert A Vandenboom Rene Leblanc Paul J Roy Brian D Jeoung Nam Ho Peters Sandra J |
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Affiliation: | Department of Kinesiology, Brock University, ON N1G 2W1, Canada. |
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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. |
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