SODIUM CURRENT AMPLITUDE INCREASES DRAMATICALLY IN HUMAN RETINAL GLIAL-CELLS DURING DISEASES OF THE EYE

Muller cells, the main macroglial cells of the retina, express several types of voltage and ligand-activated ion channels, including Na+ cha nnels. Using the whole-cell voltage-clamp technique, we studied the ex pression of Na+ currents in acutely isolated, non-cultivated human Mul ler cells from retinas of healthy organ donors and patients suffering from different eye diseases. In both types of retinas transient Na+ cu rrents could be recorded from Muller cells. The tetradotoxin-resistant Na+ currents, which were not completely blocked even at a concentrati on of 10 mu M tetrodotoxin, had a mean current density of 3.0 +/- 3.0 pA/pF (mean +/- SD, n = 10) in Muller cells from donor retinas and of 12.2 +/- 9.6 pA/pF (n = 74) in Muller cells from patient retinas. Only 33.3% of healthy but 88.4% of pathological Muller cells depicted such currents. The G(Na+)/G(K+) ratio was very high in several Muller cell s from patient retinas, such that action potential-like activity could be generated after prehyperpolarizing current injection in some of th ese cells. Apparently, the Na+ channels, due to their negative steady- state inactivation curve (V-h = -84.5 mV), do not influence the lowere d membrane potential of the pathological cells, since they are inactiv ated at these voltages. Currently, we do not have an explanation for t he increase in amplitude and frequency of Na+ currents in human Muller cells under pathological conditions. However, the up-regulation of Na + channels may mirror a basic glial response to pathological condition s, since it has also been found previously in human hippocampal astroc ytes from epileptic foci and in rat cortex stab wounds lined by an ast rocytic scar.