Cellular and subcellular specification of Na,K-ATPase alpha and beta isoforms in the postnatal development of mouse retina

The Na,K-ATPase is a dominant factor in retinal energy metabolism, and uniq ue combinations of isoforms of its alpha and beta subunits are expressed in different cell types and determine its functional properties. We used isof orm-specific antibodies and fluorescence confocal microscopy to determine t he expression of Na,K-ATPase alpha and beta subunits in the mouse and rat r etina. In the adult retina, alpha 1 was found in Muller and horizontal cell s, alpha 2 in some Muller glia, and alpha 3 in photoreceptors and all retin al neurons. beta 1 was largely restricted to horizontal, amacrine, and gang lion cells; beta 2 was largely restricted to photoreceptors, bipolar cells, and Muller glia; and beta 3 was largely restricted to photoreceptors. Phot oreceptor inner segments have the highest concentration of Na,K-ATPase in a dult retinas. Isoform distribution exhibited marked changes during postnata l development. alpha 3 and beta 2 were in undifferentiated photoreceptor so mas at birth but only later were targeted to inner segments and synaptic te rminals. beta 3, in contrast, was expressed late in photoreceptor different iation and was immediately targeted to inner segments. A high level of beta 1 expression in horizontal cells preceded migration, whereas increases in beta 2 expression in bipolar cells occurred very late, coinciding with syna ptogenesis in the inner plexiform layer. Most of the spatial specification of Na,K-ATPase isoform expression was completed before eye opening and the onset of electroretinographic responses on postnatal day 13 (P13), but quan titative increase continued until P22 in parallel with synaptogenesis.