Neurophysiological examination in relationship of glaucomatous neurodegeneration and glutamate neurotoxicity

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In 1995, we found that the activation of inositol phospholipid signaling pathway by PKC-related drugs deteriorated and the activation of adenylyl cyclase by vasoactive intestinal peptide (VIP) ameliorated glutamate neurotoxicity in retinal cultures. In 1996, we examined the dynamics of cytosolic Ca^<2+> concentration ([Ca^<2+>] i) by image analyzing system and the glutamate-induced inward current by whole-cell patch-clamp recordings, respectively, to elucidate the mechanisms of the effect of PKC-related drugs or VIP on glutamate-neurotoxicity. Using these procedure mentioned above, these drugs had no effect on glutamate-induced increase in [Ca^<2+>] i or glutamate-induced inward currents. Therefore, we speculated that PKC-related drugs and VIP affected the mechanisms of glutamate neurotoxicity at the downstream of glutamate receptor-activation.Furthermore, we found that the change of extracellular environment from pH 7.4 to acidic conditions (pH 6.0-7.0) protected cultured retinal neurons from glutamate neurotoxicity. In the electrophysiological examination using patch-clamp recording, N-methyl-D-aspartate (NMDA) receptor-activation was inhibited by extracellular acidic pH.Taken together, the acidic conditions protected cultured retinal neurons from glutamate neurotoxicity via suppression of NMDA receptor-activation.