Proliferative gliosis causes mislocation and inactivation of inwardly rectifying K(+) (Kir) channels in rabbit retinal glial cells.

Abstract Retinal glial (Muller) cells are proposed to mediate retinal potassium homeostasis predominantly by potassium transport through inwardly rectifying K + (Kir) channels. Retinal gliosis is often associated with a decrease in glial potassium conductance. To determine whether this decrease is caused by a downregulation of glial Kir channels, we investigated a rabbit model of proliferative vitreoretinopathy (PVR) which is known to be associated with proliferative gliosis. The membrane conductance of control Muller cells is characterized by large Kir currents whereas Muller cells of PVR retinas displayed an almost total absence of Kir currents. In control tissues, Kir2.1 immunoreactivity is localized in the inner stem processes and endfeet of Muller cells whereas Kir4.1 immunoreactivity is largely confined to the Muller cell endfeet. In PVR retinas, there is a mislocation of Kir channel proteins, with Kir4.1 immunoreactivity detectable in Muller cell fibers throughout the whole retina, and a decrease of immunoreactivity in the cellular endfeet. Real-time PCR analysis revealed no alteration of the Kir4.1 mRNA levels in PVR retinas as compared to the controls but a slight decrease in Kir2.1 mRNA. Western blotting showed no difference in the Kir4.1 protein content between control and PVR retinas. The data suggest that proliferative gliosis in the retina is associated with a functional inactivation of glial Kir channels that is not caused by a downregulation of the channel proteins but is associated with their mislocation in the cell membrane.