Potassium Channel Kir4.1 Macromolecular Complex in Retinal Glial Cells

M€uller cells; astrocytes A major role for M€uller cells in the retina is to buffer changes in the extracellular K1 concentration ([K1]o) resulting from light-evoked neuronal activity. The primary K1 conductance in M€uller cells is the inwardly rectifying K1 channel Kir4.1. Since this channel is constitutively active, K1 can enter or exit M€uller cells depending on the state of the [K1]o. This process of [K1]o buffering by M€uller cells (‘‘K 1 siphoning’’) is enhanced by the precise accumulation of these K1 channels at discrete subdomains of M€uller cell membranes. Specifi-cally, Kir4.1 is localized to the perivascular processes of M€uller cells in animals with vascular retinas and to the end-feet of M€uller cells in all species examined. The water chan-nel aquaporin-4 (AQP4) also appears to be important for [K1]o buffering and is expressed in M€uller cells in a very similar subcellular distribution pattern to that of Kir4.1. To gain a better understanding of how M€uller cells selectively target K1 and water channels to discrete membrane subdo-mains, we addressed the question of whether Kir4.1 and AQP4 associate with the dystrophin–glycoprotein complex (DGC) in the mammalian retina. Immunoprecipitation (IP) experiments were utilized to show that Kir4.1 and AQP4 are associated with DGC proteins in rat retina. Furthermore, AQP4 was also shown to co-precipitate with Kir4.1, suggest-ing that both channels are tethered together by the DGC in M€uller cells. This work further defines a subcellular localiza-tion mechanism in M€uller cells that facilitates [K1]o buffer-ing in the retina. VC 2005 Wiley-Liss, Inc