title: Nicorandil improves post-fatigue tension in slow skeletal muscle fibers by modulating glutathione redox state.
abstract: Fatigue is a phenomenon in which force reduction has been linked to impairment of several biochemical processes. In skeletal muscle, the ATP-sensitive potassium channels (KATP) are actively involved in myoprotection against metabolic stress. They are present in sarcolemma and mitochondria (mitoKATPchannels). K+channel openers like nicorandil has been recognized for their ability to protect skeletal muscle from ischemia-reperfusion injury, however, the effects of nicorandil on fatigue in slow skeletal muscle fibers has not been explored, being the aim of this study. Nicorandil (10 μM), improved the muscle function reversing fatigue as increased post-fatigue tension in the peak and total tension significantly with respect to the fatigued condition. However, this beneficial effect was prevented by the mitoKATPchannel blocker 5-hydroxydecanoate (5-HD, 500 μM) and by the free radical scavenger N-2-mercaptopropionyl glycine (MPG, 1 mM), but not by the nitric oxide (NO) synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 100 μM). Nicorandil also decreased lipid peroxidation and maintained both reduced glutathione (GSH) levels and an elevated GSH/GSSG ratio, whereas total glutathione (TGSH) remained unaltered during post-fatigue tension. In addition, NO production, measured through nitrite concentrations was significantly increased with nicorandil during post-fatigue tension; this increase remained unaltered in the presence of nicorandil plus L-NAME, nonetheless, this effect was reversed with nicorandil plus MPG. Hence, these results suggest that nicorandil improves the muscle function reversing fatigue in slow skeletal muscle fibers of chicken through its effects not only as a mitoKATPchannel opener but also as NO donor and as an antioxidant.
authors.affiliation: Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de julio #985 Col. Villa San Sebastián, 28040, Colima, Colima, Mexico.
authors.forename: E
authors.initials: E
authors.lastname: Sánchez-Duarte
authors.affiliation: Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de julio #985 Col. Villa San Sebastián, 28040, Colima, Colima, Mexico. rosio@ucol.mx.
authors.forename: X
authors.initials: X
authors.lastname: Trujillo
authors.affiliation: Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Francisco J. Mújica S/N, Col. Felicitas del Río, 58030, Morelia, Michoacán, Mexico.
authors.forename: C
authors.initials: C
authors.lastname: Cortés-Rojo
authors.affiliation: Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Francisco J. Mújica S/N, Col. Felicitas del Río, 58030, Morelia, Michoacán, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Saavedra-Molina
authors.affiliation: Laboratorio de Neurofisiología, Departamento de Fisiología, Centro Universitario de Ciencias dela Salud, Universidad de Guadalajara, Sierra Mojada # 950, 44340, Guadalajara, Jalisco, Mexico.
authors.forename: G
authors.initials: G
authors.lastname: Camargo
authors.affiliation: Laboratorio de Neurofisiología, Departamento de Fisiología, Centro Universitario de Ciencias dela Salud, Universidad de Guadalajara, Sierra Mojada # 950, 44340, Guadalajara, Jalisco, Mexico.
authors.forename: L
authors.initials: L
authors.lastname: Hernández
authors.affiliation: Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de julio #985 Col. Villa San Sebastián, 28040, Colima, Colima, Mexico.
authors.forename: M
authors.initials: M
authors.lastname: Huerta
authors.affiliation: Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Francisco J. Mújica S/N, Col. Felicitas del Río, 58030, Morelia, Michoacán, Mexico. rmontoya@umich.mx.
authors.forename: R
authors.initials: R
authors.lastname: Montoya-Pérez
mesh_terms: D000818:Animals; D002645:Chickens; D005978:Glutathione / Q000187:drug effects* / Q000378:metabolism; D018763:Muscle Fatigue / Q000187:drug effects*; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D018657:Muscle Fibers, Slow-Twitch / Q000502:physiology*; D009129:Muscle Tonus / Q000187:drug effects*; D020108:Nicorandil / Q000494:pharmacology* / Q000627:therapeutic use; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism
chemical_list: D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D020108:Nicorandil; D009569:Nitric Oxide; D005978:Glutathione
keywords: Fatigue; Nicorandil; Nitric oxide; Reactive oxygen species; Skeletal muscle