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

Abstract

The Na,K-ATPase is a dominant factor in retinal energy metabolism, and unique combinations of isoforms of its α and β subunits are expressed in different cell types and determine its functional properties. We used isoform-specific antibodies and fluorescence confocal microscopy to determine the expression of Na,K-ATPase α and β subunits in the mouse and rat retina. In the adult retina, α1 was found in Muller and horizontal cells, α2 in some Muller glia, and α3 in photoreceptors and all retinal neurons. β1 was largely restricted to horizontal, amacrine, and ganglion cells; β2 was largely restricted to photoreceptors, bipolar cells, and Muller glia; and β3 was largely restricted to photoreceptors. Photoreceptor inner segments have the highest concentration of Na,K-ATPase in adult retinas. Isoform distribution exhibited marked changes during postnatal development, α3 and β2 were in undifferentiated photoreceptor somas at birth but only later were targeted to inner segments and synaptic terminals. β3, in contrast, was expressed late in photoreceptor differentiation and was immediately targeted to inner segments. A high level of β1 expression in horizontal cells preceded migration, whereas increases in β2 expression in bipolar cells occurred very late, coinciding with synaptogenesis 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 quantitative increase continued until P22 in parallel with synaptogenesis.