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Using a sheep model of placental insufficiency and IUGR, we have previously demonstrated lower net total uptake of amino acids by the fetal hindlimb and lower skeletal muscle protein synthesis rates. To investigate the mechanisms underlying these changes, we tested the hypothesis that <jats:italic>ex vivo<\/jats:italic> amino acid transporter and Na<jats:sup>+<\/jats:sup>K<jats:sup>+<\/jats:sup>\u2010ATPase activity is reduced, and <jats:italic>ex vivo<\/jats:italic> ATP levels are lower in hindlimb skeletal muscle of the IUGR fetus. We developed a novel protocol to measure transporter\u2010mediated histidine uptake, system L amino acid transporter activity and Na<jats:sup>+<\/jats:sup>K<jats:sup>+<\/jats:sup>\u2010ATPase activity using sarcolemmal membranes isolated from hindlimb muscle of control (CON, <jats:italic>n<\/jats:italic>\u00a0=\u00a011\u201012) and IUGR (<jats:italic>n<\/jats:italic>\u00a0=\u00a012) late gestation fetal sheep. We also determined ATP content and the activity of insulin and mechanistic target of rapamycin (mTOR) signalling, which are involved in regulating cellular amino acid uptake and protein synthesis, by measuring the expression and phosphorylation of AKT, 4E\u2010BP1, eIF2\u03b1, AMPK\u03b1, p70 S6 kinase and rpS6 in muscle homogenates. Transporter\u2010mediated histidine uptake and system L activity were similar in control and IUGR sarcolemma, although <jats:italic>ex vivo<\/jats:italic> Na<jats:sup>+<\/jats:sup>K<jats:sup>+<\/jats:sup>\u2010ATPase activity was lower by 64% (<jats:italic>P\u00a0<\/jats:italic>=\u00a00.019) in IUGR sarcolemma. ATP content was lower by 25% (<jats:italic>P\u00a0<\/jats:italic>=\u00a00.007) in IUGR muscle. Insulin, AMPK, and mTOR signalling activity was similar in control and IUGR muscle. We speculate that reduced muscle sarcolemmal Na<jats:sup>+<\/jats:sup>K<jats:sup>+<\/jats:sup>\u2010ATPase activity and lower ATP content diminishes the sodium gradient <jats:italic>in vivo<\/jats:italic>, resulting in a reduced driving force for sodium\u2010dependent transporters and subsequently lower muscle amino acid uptake.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp278933","type":"journal-article","created":{"date-parts":[[2020,1,7]],"date-time":"2020-01-07T12:01:14Z","timestamp":1578398474000},"page":"1625-1639","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Reduced Na<sup>+<\/sup>K<sup>+<\/sup>\u2010ATPase activity may reduce amino acid uptake in intrauterine growth restricted fetal sheep muscle despite unchanged <i>ex vivo<\/i> amino acid transporter activity"],"prefix":"10.1113","volume":"598","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8517-2463","authenticated-orcid":false,"given":"Jane","family":"Stremming","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Colorado Anschutz Medical Campus  Aurora CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Jansson","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Colorado Anschutz Medical Campus  Aurora CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa L","family":"Powell","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado Anschutz Medical Campus  Aurora CO USA"},{"name":"Department of Obstetrics and Gynecology University of Colorado Anschutz Medical Campus  Aurora CO 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