title: KATP channel deficiency in mouse FDB causes an impairment of energy metabolism during fatigue.
abstract: The skeletal muscle ATP-sensitive K+(KATP) channel is crucial in preventing fiber damage and contractile dysfunction, possibly by preventing damaging ATP depletion. The objective of this study was to investigate changes in energy metabolism during fatigue in wild-type and inwardly rectifying K+channel (Kir6.2)-deficient (Kir6.2-/-) flexor digitorum brevis (FDB), a muscle that lacks functional KATPchannels. Fatigue was elicited with one tetanic contraction every second. Decreases in ATP and total adenylate levels were significantly greater in wild-type than Kir6.2-/-FDB during the last 2 min of the fatigue period. Glycogen depletion was greater in Kir6.2-/-FDB for the first 60 s, but not by the end of the fatigue period, while there was no difference in glucose uptake. The total amount of glucosyl units entering glycolysis was the same in wild-type and Kir6.2-/-FDB. During the first 60 s, Kir6.2-/-FDB generated less lactate and more CO2; in the last 120 s, Kir6.2-/-FDB stopped generating CO2and produced more lactate. The ATP generated during fatigue from phosphocreatine, glycolysis (lactate), and oxidative phosphorylation (CO2) was 3.3-fold greater in Kir6.2-/-than wild-type FDB. Because ATP and total adenylate were significantly less in Kir6.2-/-FDB, it is suggested that Kir6.2-/-FDB has a greater energy deficit, despite a greater ATP production, which is further supported by greater glucose uptake and lactate and CO2production in Kir6.2-/-FDB during the recovery period. It is thus concluded that a lack of functional KATPchannels results in an impairment of energy metabolism.
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Kyle
authors.initials: K
authors.lastname: Scott
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Maria
authors.initials: M
authors.lastname: Benkhalti
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Calvert
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Paquette
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Li
authors.initials: L
authors.lastname: Zhen
authors.affiliation: Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Harper
authors.affiliation: Newborn Screening Ontario, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; and Faculty of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
authors.forename: Osama Y
authors.initials: OY
authors.lastname: Al-Dirbashi
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; jmrenaud@uottawa.ca.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Renaud
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D006019:Glycolysis / Q000502:physiology; D054086:KATP Channels / Q000172:deficiency* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000502:physiology; D018763:Muscle Fatigue / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D000099161:Kcnj11 Channel
chemical_list: D000255:Adenosine Triphosphate; D002245:Carbon Dioxide; D054086:KATP Channels; D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel
keywords: CO2; glucose; glycogen; lactate