Role of glial K+ channels in ontogeny and gliosis: A hypothesis based upon studies on Muller cells

Abstract

The electrophysiological properties of Muller cells, the principal glial cells of the retina, are determined by several types of K+ conductances. Both the absolute and the relative activities of the individual types of K+ channels undergo important changes in the course of ontogenetic development and during gliosis. Although immature Muller cells express inwardly rectifying K+ (K(IR)) currents at a very low density, the membrane of normal mature Muller cells is predominated by the K(IR) conductance. The K(IR) channels mediate spatial buffering K+ currents and maintain a stable hyperpolarized membrane potential necessary for various glial-neuronal interactions. During 'conservative' (i.e., non-proliferative) reactive gliosis, the K(IR) conductance of Muller cells is moderately reduced and the cell membrane is slightly depolarized; however, when gliotic Muller cells become proliferative, their K(IR) conductances are dramatically down-regulated; this is accompanied by an increased activity of Ca2+-activated K+ channels and by a conspicuous unstability of their membrane potential. The resultant variations of the membrane potential may increase the activity of depolarization-activated K+, Na+ and Ca2+ channels. It is concluded that in respect to their K+ current pattern, mature Muller cells pass through a process of dedifferentiation before proliferative activity is initiated.