title: Membrane lipid rafts are disturbed in the response of rat skeletal muscle to short-term disuse.
abstract: Marked loss of skeletal muscle mass occurs under various conditions of disuse, but the molecular and cellular mechanisms leading to atrophy are not completely understood. We investigate early molecular events that might play a role in skeletal muscle remodeling during mechanical unloading (disuse). The effects of acute (6-12 h) hindlimb suspension on the soleus muscles from adult rats were examined. The integrity of plasma membrane lipid rafts was tested utilizing cholera toxin B subunit or fluorescent sterols. In addition, resting intracellular Ca2+level was analyzed. Acute disuse disturbed the plasma membrane lipid-ordered phase throughout the sarcolemma and was more pronounced in junctional membrane regions. Ouabain (1 µM), which specifically inhibits the Na-K-ATPase α2 isozyme in rodent skeletal muscles, produced similar lipid raft changes in control muscles but was ineffective in suspended muscles, which showed an initial loss of α2 Na-K-ATPase activity. Lipid rafts were able to recover with cholesterol supplementation, suggesting that disturbance results from cholesterol loss. Repetitive nerve stimulation also restores lipid rafts, specifically in the junctional sarcolemma region. Disuse locally lowered the resting intracellular Ca2+concentration only near the neuromuscular junction of muscle fibers. Our results provide evidence to suggest that the ordering of lipid rafts strongly depends on motor nerve input and may involve interactions with the α2 Na-K-ATPase. Lipid raft disturbance, accompanied by intracellular Ca2+dysregulation, is among the earliest remodeling events induced by skeletal muscle disuse.
authors.affiliation: Department of Normal Physiology, Kazan State Medical University, Kazan, Russia.
authors.forename: Alexey M
authors.initials: AM
authors.lastname: Petrov
authors.affiliation: Department of General Physiology, St. Petersburg State University, St. Petersburg, Russia.
authors.forename: Violetta V
authors.initials: VV
authors.lastname: Kravtsova
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Matchkov
authors.affiliation: Department of General Physiology, St. Petersburg State University, St. Petersburg, Russia.
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Vasiliev
authors.affiliation: Department of Normal Physiology, Kazan State Medical University, Kazan, Russia.
authors.forename: Andrey L
authors.initials: AL
authors.lastname: Zefirov
authors.affiliation: Department of Molecular Medicine and Surgery, Integrative Physiology, Karolinska Institutet, Stockholm, Sweden; and.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Chibalin
authors.affiliation: Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Heiny
authors.affiliation: Department of General Physiology, St. Petersburg State University, St. Petersburg, Russia; iikrivoi@gmail.com.
authors.forename: Igor I
authors.initials: II
authors.lastname: Krivoi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002784:Cholesterol / Q000378:metabolism*; D019417:Hindlimb Suspension; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism* / Q000473:pathology*; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology*; D020966:Muscular Disorders, Atrophic / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002784:Cholesterol; D002118:Calcium
keywords: cholesterol; hindlimb suspension; intracellular calcium; lipid rafts; skeletal muscle disuse