title: Distinct α2 Na,K-ATPase membrane pools are differently involved in early skeletal muscle remodeling during disuse.
abstract: The Na,K-ATPase is essential for the contractile function of skeletal muscle, which expresses the α1 and α2 subunit isoforms of Na,K-ATPase. The α2 isozyme is predominant in adult skeletal muscles and makes a greater contribution in working compared with noncontracting muscles. Hindlimb suspension (HS) is a widely used model of muscle disuse that leads to progressive atrophy of postural skeletal muscles. This study examines the consequences of acute (6-12 h) HS on the functioning of the Na,K-ATPase α1 and α2 isozymes in rat soleus (disused) and diaphragm (contracting) muscles. Acute disuse dynamically and isoform-specifically regulates the electrogenic activity, protein, and mRNA content of Na,K-ATPase α2 isozyme in rat soleus muscle. Earlier disuse-induced remodeling events also include phospholemman phosphorylation as well as its increased abundance and association with α2 Na,K-ATPase. The loss of α2 Na,K-ATPase activity results in reduced electrogenic pump transport and depolarized resting membrane potential. The decreased α2 Na,K-ATPase activity is caused by a decrease in enzyme activity rather than by altered protein and mRNA content, localization in the sarcolemma, or functional interaction with the nicotinic acetylcholine receptors. The loss of extrajunctional α2 Na,K-ATPase activity depends strongly on muscle use, and even the increased protein and mRNA content as well as enhanced α2 Na,K-ATPase abundance at this membrane region after 12 h of HS cannot counteract this sustained inhibition. In contrast, additional factors may regulate the subset of junctional α2 Na,K-ATPase pool that is able to recover during HS. Notably, acute, low-intensity muscle workload restores functioning of both α2 Na,K-ATPase pools. These results demonstrate that the α2 Na,K-ATPase in rat skeletal muscle is dynamically and acutely regulated by muscle use and provide the first evidence that the junctional and extrajunctional pools of the α2 Na,K-ATPase are regulated differently.
authors.affiliation: Department of General Physiology, St. Petersburg State University, St. Petersburg 199034, Russia.
authors.forename: Violetta V
authors.initials: VV
authors.lastname: Kravtsova
authors.affiliation: Department of Normal Physiology, Kazan State Medical University, Kazan 420012, Russia.
authors.forename: Alexey M
authors.initials: AM
authors.lastname: Petrov
authors.affiliation: Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark.
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Matchkov
authors.affiliation: Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, 8240 Risskov, Denmark.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Bouzinova
authors.affiliation: Department of General Physiology, St. Petersburg State University, St. Petersburg 199034, Russia.
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Vasiliev
authors.affiliation: Integrative Physiology, Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Boubacar
authors.initials: B
authors.lastname: Benziane
authors.affiliation: Department of Normal Physiology, Kazan State Medical University, Kazan 420012, Russia.
authors.forename: Andrey L
authors.initials: AL
authors.lastname: Zefirov
authors.affiliation: Integrative Physiology, Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
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, OH 45267.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Heiny
authors.affiliation: Department of General Physiology, St. Petersburg State University, St. Petersburg 199034, Russia iikrivoi@gmail.com.
authors.forename: Igor I
authors.initials: II
authors.lastname: Krivoi
mesh_terms: D000818:Animals; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D010750:Phosphoproteins; D011978:Receptors, Nicotinic; C069141:phospholemman; D000254:Sodium-Potassium-Exchanging ATPase