Dessi F, Charriaut-Marlangue C, Ben-Ari Y
INSERM U29, Paris, France.
Brain Res. 1994 Jul 4;650(1):49-55. doi: 10.1016/0006-8993(94)90205-4.
The relative contribution of sodium, chloride and calcium ions in the neuronal death induced by glutamate is controversial. We have therefore reassessed the effects of extracellular ion substitution on glutamate-induced neuronal death in cerebellar granule cell culture. Sodium or chloride substitution by impermeant ions prevented the initial swelling observed after glutamate exposure (100 microM, 15 min) in balanced salt solution but did not prevent the progressive degeneration of cerebellar neurons over the next few hours. In low calcium medium, glutamate exposure also led to degeneration of granule neurons. In contrast, sodium or chloride substitution and calcium omission prevented both the initial swelling and the delayed neuronal death after glutamate exposure. These morphological observations were confirmed both by measurement of the intracellular water space with [3H]methylglucose and by quantification of cell viability by 3-(4,5-dimethylthiazol-2-yl-)-2,5-diphenyl tetrazolium bromide (MTT) staining. We conclude that glutamate-induced neuronal death is mediated by two distinct components: a calcium-independent sodium-chloride dependent component and a calcium-dependent component. Each one of these components leads to the death of cerebellar neurons after glutamate exposure.
在谷氨酸诱导的神经元死亡中，钠离子、氯离子和钙离子的相对作用存在争议。因此，我们重新评估了细胞外离子替代对小脑颗粒细胞培养物中谷氨酸诱导的神经元死亡的影响。用非渗透性离子替代钠离子或氯离子可防止在平衡盐溶液中谷氨酸暴露（100微摩尔，15分钟）后观察到的初始肿胀，但不能防止小脑神经元在接下来的几个小时内逐渐退化。在低钙培养基中，谷氨酸暴露也会导致颗粒神经元退化。相反，钠离子或氯离子替代以及去除钙离子可防止谷氨酸暴露后的初始肿胀和延迟的神经元死亡。通过用[³H]甲基葡萄糖测量细胞内水空间以及通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四氮唑（MTT）染色对细胞活力进行定量，证实了这些形态学观察结果。我们得出结论，谷氨酸诱导的神经元死亡由两个不同的成分介导：一个是不依赖钙而依赖氯化钠的成分，另一个是依赖钙的成分。谷氨酸暴露后，这些成分中的每一个都会导致小脑神经元死亡。
