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

The electrophysiological properties of Muller cells, the principal glial ce lls of the retina, are determined by several types of K+ conductances. Both the absolute and the relative activities of the individual types of K+ cha nnels undergo important changes in the course of ontogenetic development an d during gliosis. Although immature Muller cells express inwardly rectifyin g K+ (K-IR) currents at a very low density, the membrane of normal mature M uller cells is predominated by the K-IR conductance. The K-IR channels medi ate spatial buffering K+ currents and maintain a stable hyperpolarized memb rane potential necessary for various glial-neuronal interactions. During "c onservative" (i.e., non-proliferative) reactive gliosis, the K-IR conductan ce 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 un stability of their membrane potential. The resultant variations of the memb rane potential may increase the activity of depolarization-activated K+, Na + and Ca2+ channels. It is concluded that in respect to their K+ current pa ttern, mature Muller cells pass through a process of dedifferentiation befo re proliferative activity is initiated. GLIA 29:35-44, 2000. (C) 2000 Wiley -Liss, Inc.