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Pyruvate dehydrogenase (PDH) activity in response to skeletal muscle contraction at two stimulation frequencies in PDH kinase 4 knockout mice
Author(s) -
Martin Dale Marie,
Harris R A,
Vandenboom R,
LeBlanc P J,
Roy B D,
Jeoung N H,
Peters Sandra J
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1355-c
Subject(s) - pdk4 , pyruvate dehydrogenase complex , contraction (grammar) , skeletal muscle , stimulation , endocrinology , medicine , chemistry , muscle contraction , pyruvate dehydrogenase kinase , biology , biochemistry , enzyme
Pyruvate dehydrogenase (PDH) plays a key role in carbohydrate oxidation within skeletal muscle. PDH is deactivated by PDH kinase (PDK), with the predominant skeletal muscle isoforms being PDK2 and 4. Although PDK2 is most abundant under normal conditions, PDK4 expression accounts for the majority of PDH deactivation following starvation and high fat diets, but little is known about what role PDK4 plays during an acute bout of muscle contraction. This study examined the differential activation of PDH (PDHa) during electrically stimulated contraction of fast‐twitch muscle from PDK4 knockout mice (KO) and wild type (WT) littermates. Extensor digitorum longus muscles were removed from KO and WT after a 24h fast (n=5) and placed in an organ bath (25°C) with the distal tendon fixed to a stationary hook; proximal tendon attached to a force transducer. Muscles were incubated for 30 min (Rest) and then stimulated to contract at low (10 Hz) or higher intensity (40 Hz) for 3 min. Force produced by KO and WT muscle was the same throughout the stimulation period. PDHa activity increased compared to rest at both intensities (KO: Rest, 0.88±0.19; 10Hz, 1.70±0.14; 40Hz, 3.75±0.14; WT: Rest, 0.34±0.12; 10Hz, 0.83±0.14 (p=0.059); 40Hz, 1.82±0.14 mmol/min/kg ww; p<0.001). Between groups, PDHa activity in KO muscle was greater than WT at all intensities. Therefore, the absence of PDK4 resulted in much higher PDHa activity at rest and both contraction intensities, suggesting an important role of PDK4 in regulating contraction‐mediated carbohydrate oxidation. Supported by NSERC and NIH (RAH)