The Na,K-ATPase alpha 2 isoform is expressed in neurons, and its absence disrupts neuronal activity in newborn mice.
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.
Moseley
Amy E
AE
Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45267, USA.
Lieske
Steve P
SP
Wetzel
Randall K
RK
James
Paul F
PF
He
Suiwen
S
Shelly
Daniel A
DA
Paul
Richard J
RJ
Boivin
Gregory P
GP
Witte
David P
DP
Ramirez
Jan Marino
JM
Sweadner
Kathleen J
KJ
Lingrel
Jerry B
JB
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
D007527:Isoenzymes; C401838:Atp1a2 protein, mouse; D000254:Sodium-Potassium-Exchanging ATPase