title: Na+/K+ ATPase α1 and α3 isoforms are differentially expressed in α- and γ-motoneurons.
abstract: The Na(+)/K(+) ATPase (NKA) is an essential membrane protein underlying the membrane potential in excitable cells. Transmembrane ion transport is performed by the catalytic α subunits (α1-4). The predominant subunits in neurons are α1 and α3, which have different affinities for Na(+) and K(+), impacting on transport kinetics. The exchange rate of Na(+)/K(+) markedly influences the activity of the neurons expressing them. We have investigated the distribution and function of the main isoforms of the α subunit expressed in the mouse spinal cord. NKAα1 immunoreactivity (IR) displayed restricted labeling, mainly confined to large ventral horn neurons and ependymal cells. NKAα3 IR was more widespread in the spinal cord, again being observed in large ventral horn neurons, but also in smaller interneurons throughout the dorsal and ventral horns. Within the ventral horn, the α1 and α3 isoforms were mutually exclusive, with the α3 isoform in smaller neurons displaying markers of γ-motoneurons and α1 in α-motoneurons. The α3 isoform was also observed within muscle spindle afferent neurons in dorsal root ganglia with a higher proportion at cervical versus lumbar regions. We confirmed the differential expression of α subunits in motoneurons electrophysiologically in neonatal slices of mouse spinal cord. γ-Motoneurons were excited by bath application of low concentrations of ouabain that selectively inhibit NKAα3 while α-motoneurons were insensitive to these low concentrations. The selective expression of NKAα3 in γ-motoneurons and muscle spindle afferents, which may affect excitability of these neurons, has implications in motor control and disease states associated with NKAα3 dysfunction.
authors.affiliation: School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Edwards
authors.forename: Gareth
authors.initials: G
authors.lastname: Bruce
authors.forename: Charlotte
authors.initials: C
authors.lastname: Lawrenson
authors.forename: Laura
authors.initials: L
authors.lastname: Howe
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Clapcote
authors.forename: Susan A
authors.initials: SA
authors.lastname: Deuchars
authors.forename: Jim
authors.initials: J
authors.lastname: Deuchars
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D000870:Anterior Horn Cells / Q000187:drug effects / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000201:enzymology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009047:Motor Neurons, Gamma / Q000187:drug effects / Q000201:enzymology*; D010042:Ouabain / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010320:Parvalbumins / Q000378:metabolism; D018408:Patch-Clamp Techniques; D012702:Serotonin Antagonists / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000201:enzymology; D014363:Tryptamines / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D010320:Parvalbumins; D012702:Serotonin Antagonists; D014363:Tryptamines; C085632:L 694247; D010042:Ouabain; C526097:Atp1a3 protein, mouse; C497344:Atp1a1 protein, mouse; D000254:Sodium-Potassium-Exchanging ATPase