Finkbeiner S, Stevens C F
Section of Molecular Neurobiology, Yale University School of Medicine, New Haven, CT 06510.
Proc Natl Acad Sci U S A. 1988 Jun;85(11):4071-4. doi: 10.1073/pnas.85.11.4071.
The role of the N-methyl-D-aspartate receptor channel in glutamate neurotoxicity was investigated in cultured hippocampal neurons of the CA1 region. An equation, the survival function, was developed to quantify the effects of putative modulators of neurotoxicity. 2-Amino-5-phosphonovaleric acid (30 microM) reduced the neuronal sensitivity to glutamate by a factor greater than 20, whereas glycine (1 microM) enhanced it by a factor of 7.5 +/- 2.5. Neurons were protected by increasing Mg2+ concentrations in a predictable way based on the ion's ability to block the N-methyl-D-aspartate channel. These findings provide a quantitative basis for the assessment of various neuroprotective agents and add further support to the hypothesis that the N-methyl-D-aspartate channel is central to glutamate neurotoxicity.
在CA1区培养的海马神经元中研究了N-甲基-D-天冬氨酸受体通道在谷氨酸神经毒性中的作用。开发了一个方程，即生存函数，以量化假定的神经毒性调节剂的作用。2-氨基-5-磷酸戊酸（30微摩尔）使神经元对谷氨酸的敏感性降低了20倍以上，而甘氨酸（1微摩尔）使其增强了7.5±2.5倍。根据镁离子阻断N-甲基-D-天冬氨酸通道的能力，以可预测的方式通过增加镁离子浓度来保护神经元。这些发现为评估各种神经保护剂提供了定量依据，并进一步支持了N-甲基-D-天冬氨酸通道是谷氨酸神经毒性核心的假说。
