title: Treadmill running causes significant fiber damage in skeletal muscle of KATP channel-deficient mice.
abstract: Although it has been suggested that the ATP-sensitive K(+) (K(ATP)) channel protects muscle against function impairment, most studies have so far given little evidence for significant perturbation in the integrity and function of skeletal muscle fibers from inactive mice that lack K(ATP) channel activity in their cell membrane. The objective was, therefore, to test the hypothesis that K(ATP) channel-deficient skeletal muscle fibers become damaged when mice are subjected to stress. Wild-type and K(ATP) channel-deficient mice (Kir6.2(-/-) mice) were subjected to 4-5 wk of treadmill running at either 20 m/min with 0 degrees inclination or at 24 m/min with 20 degrees uphill inclination. Muscles of all wild-type mice and of nonexercised Kir6.2(-/-) mice had very few fibers with internal nuclei. After 4-5 wk of treadmill running, there was little evidence for connective tissues and mononucleated cells in Kir6.2(-/-) hindlimb muscles, whereas the number of fibers with internal nuclei, which appear when damaged fibers are regenerated by satellite cells, was significantly higher in Kir6.2(-/-) than wild-type mice. Between 5% and 25% of the total number of fibers in Kir6.2(-/-) extensor digitum longus, plantaris, and tibialis muscles had internal nuclei, and most of such fibers were type IIB fibers. Contrary to hindlimb muscles, diaphragms of Kir6.2(-/-) mice that had run at 24 m/min had few fibers with internal nuclei, but mild to severe fiber damage was observed. In conclusion, the study provides for the first time evidence 1) that the K(ATP) channels of skeletal muscle are essential to prevent fiber damage, and thus muscle dysfunction; and 2) that the extent of fiber damage is greater and the capacity of fiber regeneration is less in Kir6.2(-/-) diaphragm muscles compared with hindlimb muscles.
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Thabet
authors.forename: T
authors.initials: T
authors.lastname: Miki
authors.forename: S
authors.initials: S
authors.lastname: Seino
authors.forename: J-M
authors.initials: JM
authors.lastname: Renaud
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000473:pathology; D006984:Hypertrophy; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000473:pathology*; D018482:Muscle, Skeletal / Q000293:injuries / Q000473:pathology*; D005082:Physical Exertion / Q000502:physiology*; D015221:Potassium Channels / Q000172:deficiency* / Q000235:genetics
chemical_list: D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel