title: The Na,K-ATPase alpha 2 isoform is expressed in neurons, and its absence disrupts neuronal activity in newborn mice.
abstract: Na,K-ATPase is an ion transporter that impacts neural and glial physiology by direct electrogenic activity and the modulation of ion gradients. Its three isoforms in brain have cell-type and development-specific expression patterns. Interestingly, our studies demonstrate that in late gestation, the alpha2 isoform is widely expressed in neurons, unlike in the adult brain, in which alpha2 has been shown to be expressed primarily in astrocytes. This unexpected distribution of alpha2 isoform expression in neurons is interesting in light of our examination of mice lacking the alpha2 isoform which fail to survive after birth. These animals showed no movement; however, defects in gross brain development, muscle contractility, neuromuscular transmission, and lung development were ruled out. Akinesia suggests a primary neuronal defect and electrophysiological recordings in the pre-Bötzinger complex, the brainstem breathing center, showed reduction of respiratory rhythm activity, with less regular and smaller population bursts. These data demonstrate that the Na,K-ATPase alpha2 isoform could be important in the modulation of neuronal activity in the neonate.
authors.affiliation: Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45267, USA.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Moseley
authors.forename: Steve P
authors.initials: SP
authors.lastname: Lieske
authors.forename: Randall K
authors.initials: RK
authors.lastname: Wetzel
authors.forename: Paul F
authors.initials: PF
authors.lastname: James
authors.forename: Suiwen
authors.initials: S
authors.lastname: He
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Shelly
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Paul
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Boivin
authors.forename: David P
authors.initials: DP
authors.lastname: Witte
authors.forename: Jan Marino
authors.initials: JM
authors.lastname: Ramirez
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Sweadner
authors.forename: Jerry B
authors.initials: JB
authors.lastname: Lingrel
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000201:enzymology* / Q000254:growth & development; D004594:Electrophysiology; D018507:Gene Expression Regulation, Developmental; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D009474:Neurons / Q000201:enzymology* / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D007527:Isoenzymes; C401838:Atp1a2 protein, mouse; D000254:Sodium-Potassium-Exchanging ATPase