Neurophysiological examination in relationship of glaucomatous neurodegeneration and glutamate neurotoxicity

1995年，我们发现PKC相关药物对肌醇磷脂信号通路的激活恶化，血管活性肠肽（VIP）对腺苷酸环化酶的激活减轻了视网膜培养中谷氨酸的神经毒性。1996年，我们分别用图像分析系统和全细胞膜片钳技术观察了细胞内Ca^<2 +>浓度（[Ca^<2+] i）的动态变化和谷氨酸诱导的内向电流，以阐明PKC相关药物或VIP对谷氨酸神经毒性的作用机制。使用上述方法，这些药物对谷氨酸诱导的[Ca^2+] i增加或谷氨酸诱导的内向电流没有影响。因此，我们推测PKC相关药物和VIP在谷氨酸受体激活的下游影响谷氨酸神经毒性的机制，并发现细胞外环境从pH 7.4到酸性（pH 6.0-7.0）的改变保护了培养的视网膜神经元免受谷氨酸神经毒性的影响。在膜片钳记录的电生理检查中，N-甲基-D-天冬氨酸（NMDA）受体激活被细胞外酸性pH抑制。总之，酸性条件通过抑制NMDA受体激活来保护培养的视网膜神经元免受谷氨酸神经毒性。

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.