Altered membrane physiology in Müller glial cells after transient ischemia of the rat retina

Abstract

Inwardly rectifying K+ (Kir) channels have been implicated in the mediation of retinal K+ homeostasis by Muller glial cells. To assess possible involvement of altered glial K+ channel expression in ischemia-reperfusion injury, transient retinal ischemia was induced in rat eyes. Acutely isolated Muller cells from postischemic retinae displayed a fast downregulation of their Kir currents, which began within 1 day and reached a maximum at 3 days of reperfusion, with a peak decrease to 20% as compared with control. This strong decrease of Kir currents was accompanied by an increase of the incidence of cells which displayed depolarization-evoked fast transient (A-type) K+ currents. While no cell from untreated control rats expressed A-type K+ currents, all cells investigated from 3- and 7-day postischemic retinae displayed such currents. An increased incidence of cells displaying fast transient Na+ currents was observed at 7 days after ischemia. These results suggest a role of altered glial Kir channel expression in postischemic neuronal degeneration via disturbance of retinal K+ siphoning.

Diabetes Alters Osmotic Swelling Characteristics and Membrane Conductance of Glial Cells in Rat Retina

“…Electrophysiological recordings. Mü ller glial cells were acutely isolated as previously described (14). The whole-cell currents of Mü ller cells were recorded using the Axopatch 200A amplifier (Axon Instruments, Foster City, CA) and the ISO-2 computer program (MFK, Niedernhausen, Germany).…”

“…We have recently shown with rat models of retinal ischemia reperfusion and uveoretinitis that the osmotic swelling characteristics of Mü ller glial cells are significantly altered under both conditions: acute application of a hypotonic bath solution (a situation that resembles hypoxia-induced cytotoxic edema in the brain) induced swelling of glial cells in slices of postischemic and inflamed retinas but had no effect on the volume of cells in control retinas (12,13). Osmotic glial cell swelling has been linked to the decrease of the main K ϩ conductance of the cells (i.e., currents through Kir4.1 channels) (12,14) and to endogenous formation of arachidonic acid in response to osmotic stress (15). An alteration of K ϩ channels in cells of postischemic and inflamed retinas disturbs the rapid release of K ϩ ions in response to arachidonic acid-induced intracellular Na ϩ overload, resulting in cell swelling (15).…”

Glia: the fulcrum of brain diseases

“…Further progression of reactive gliosis is accompanied by a dedifferentiation of the cells; a key step consists in a downregulation and redistribution of K þ channels in the glial cell plasma membrane. 45 Particularly, the K ir 4.1 are no longer enriched in the perivascular and vitreal endfoot membranes of Mü ller cells, 51 and the K þ conductance of the cell membrane at potentials negative to -40 mV is strongly reduced or even completely missing. 51 This is accompanied by a loss of the negative resting membrane potential of the cells; such reactive Mü ller cells display stochastically scattered membrane potentials up to levels as low as À20 mV.…”

“…45 Particularly, the K ir 4.1 are no longer enriched in the perivascular and vitreal endfoot membranes of Mü ller cells, 51 and the K þ conductance of the cell membrane at potentials negative to -40 mV is strongly reduced or even completely missing. 51 This is accompanied by a loss of the negative resting membrane potential of the cells; such reactive Mü ller cells display stochastically scattered membrane potentials up to levels as low as À20 mV. 45,51 Thus, the reactive downregulation of K þ channels constitutes a switch from neuroprotective functioning of mature glia to a 'private live' of dedifferentiated glial cells which now abandon neurones to an increasing chaos of their waste products.…”

“…51 This is accompanied by a loss of the negative resting membrane potential of the cells; such reactive Mü ller cells display stochastically scattered membrane potentials up to levels as low as À20 mV. 45,51 Thus, the reactive downregulation of K þ channels constitutes a switch from neuroprotective functioning of mature glia to a 'private live' of dedifferentiated glial cells which now abandon neurones to an increasing chaos of their waste products. The neurones continue to release K þ and glutamate neither of which can be buffered by the Mü ller cells any longer (Figure 2b, I and II), owing to insufficient K þ conductance and altered membrane potential (i.e., missing driving force for glutamate uptake).…”