Genetic inactivation of an inwardly rectifying potassium channel (Kir4.1 subunit) in mice: Phenotypic impact in retina

The inwardly rectifying potassium channel Kir4.1 has been suggested to unde rlie the principal K+ conductance of mammalian Muller cells and to particip ate in the generation of field potentials and regulation of extracellular K + in the retina. To further assess the role of Kir4.1 in the retina, we gen erated a mouse line with targeted disruption of the Kir4.1 gene (Kir4.1 -/- ). Muller cells from Kir4.1 -/- mice were not labeled with an anti-Kir4.1 a ntibody, although they appeared morphologically normal when stained with an anti-glutamine synthetase antibody. In contrast, in Muller cells from wild -type littermate (Kir4.1 +/+) mice, Kir4.1 was present and localized to the proximal endfeet and perivascular processes. In situ whole-cell patch-clam p recordings showed a 10-fold increase in the input resistance and a large depolarization of Kir4.1 -/- Muller cells compared with Kir4.1 +/+ cells. T he slow PIII response of the light-evoked electroretinogram (ERG), which is generated by K+ fluxes through Muller cells, was totally absent in retinas from Kir4.1 -/- mice. The b-wave of the ERG, in contrast, was spared in th e null mice. Overall, these results indicate that Kir4.1 is the principal K + channel subunit expressed in mouse Muller glial cells. The highly regulat ed localization and the functional properties of Kir4.1 in Muller cells sug gest the involvement of this channel in the regulation of extracellular Kin the mouse retina.