MODULATION OF N-METHYL-D-ASPARTATE RECEPTOR ACTIVITY BY OXIDATIVE STRESS CONDITIONS IN CHICK RETINAL CELLS

The effect of oxidative stress, induced by ascorbate (1.5 mM)/Fe2+ (7. 5 mu M), on the cellular responses to N-methyl-D-aspartate (NMDA) rece ptor activation was evaluated by measuring the release of [H-3]GABA in duced by NMDA from cultured retina cells. In retina cells submitted to oxidative stress the [H-3]GABA release evoked by NMDA, in a medium co ntaining physiological concentrations of Mg2+ (1.6 mM) and K+ (4 mM), was significantly higher than in control cells. The [H-3]GABA release evoked by NMDA was potentiated by glycine and was abolished by MK-801, suggesting that the [H-3]GABA release was due to NMDA receptor activa tion. The increased effect of NMDA in peroxidized cells was significan tly reduced by TTX, suggesting that the higher cellular responses to t he activation of NMDA receptors are due to a hyperexcitability of reti na cells submitted to oxidative stress. No significant differences wer e found between the average resting membrane potential of control and peroxidized cells. However, membrane potential is more tightly regulat ed by K+-channels sensitive to 4-aminopyridine (100 mu M), alpha-dendr otoxin (100 nM) and gamma-dendrotoxin (100 nM) under oxidative stress.