Takadera T, Shimada Y, Mohri T
2nd Division of the Research Laboratory for Development of Medicine, Hokuriku University, Kanazawa, Japan.
Brain Res. 1992 Feb 14;572(1-2):126-31. doi: 10.1016/0006-8993(92)90460-q.
The effect of extracellular pH (pHo) on the excitotoxicity of N-methyl-D-aspartate (NMDA) in cultured rat cortical cells was studied. Treatment of cells with 500 microM NMDA for 15 min at various pH's in a range from 6.5 to 8.0 progressively enhanced staining with Trypan blue and release of lactate dehydrogenase with increased pH after 18 h of culture following treatment. The cytotoxic effect of high concentration of K+ (40 mM) or veratridine (10 microM) was also directly related to the increase in pHo. Free calcium accumulation in cells on addition of NMDA increased parallel to pHo. Changes in intracellular pH were estimated to be minor compared with extracellular changes. Specific NMDA antagonists could block both the NMDA- and membrane depolarization-induced neurotoxicity and calcium accumulation completely. These results suggest that the proton concentration outside of cells attenuates NMDA-induced neurotoxicity by blocking calcium accumulation.
研究了细胞外pH值（pHo）对培养的大鼠皮层细胞中N-甲基-D-天冬氨酸（NMDA）兴奋性毒性的影响。在pH值范围为6.5至8.0的不同条件下，用500微摩尔/升的NMDA处理细胞15分钟，在处理后的18小时培养期内，随着pH值升高，锥虫蓝染色逐渐增强，乳酸脱氢酶释放增加。高浓度钾离子（40毫摩尔/升）或藜芦碱（10微摩尔/升）的细胞毒性作用也与pHo的升高直接相关。添加NMDA后细胞内游离钙的积累与pHo平行增加。与细胞外变化相比，细胞内pH值的变化估计较小。特异性NMDA拮抗剂可以完全阻断NMDA和膜去极化诱导的神经毒性以及钙积累。这些结果表明，细胞外的质子浓度通过阻断钙积累来减轻NMDA诱导的神经毒性。
