外向钾电流在谷氨酸引起的神经元损伤中的作用

The involvement of outward K^+ currents in glutamate-induced neuronal damage

目的:探讨谷氨酸通过(NMDA)受体对外向钾电流的影响以及引起神经元损伤的作用机制。方法:以分离出的孕18d SD大鼠胎鼠的皮层神经元作为实验对象,分为对照组和谷氨酸处理组,利用全细胞膜片钳的方法记录外向钾电流的变化,通过细胞形态学和TUNEL的方法分别观察谷氨酸处理后神经元的损伤情况。结果:谷氨酸能明显引起外向钾电流的增大,而NMDA受体抑制剂MK-801明显抑制由谷氨酸引起的外向钾电流的增大。形态学以及TUNEL实验研究表明,谷氨酸明显引起神经元的损伤(P<0.01),而MK-801、钾通道抑制剂TEA以及高浓度的外钾溶液能明显减缓由谷氨酸引起的细胞损伤(P<0.01)。结论:外向钾电流参与了谷氨酸引起的神经元的损伤,但其机制仍需进一步的探讨。

Objective：To explore the effects of glutamate and the NMDA receptor on the outward K ＋ currents,and illustrate the mechanisms for glutamate induced neuronal damage.Methods：Neurons were collected from18-day-old embryonic rats in the present work and were divided into two groups：the control and glutamate treated group.The currents were recorded by performing the whole cell patch clamp,and subsequently the cell morphous as well as neuron apoptosis were evaluated by morphology and TUNEL assay.Results：Glutamate obviously increased the outward K＋ currents and MK-801,the NMDA receptor antagonist,significantly alleviated the outward K＋ currents.The morphology and TUNEL results revealed that the treatment of glutamate resulted in neuronal damage（P〈0.01） while MK-801,the blocker of K＋ channel TEA,as well as high concentration of K＋ solution substantially reduced the cell damage（P〈0.01）.Conclusion：The outward K＋ currents were involved in neuronal damage induced by glutamate,and the mechanisms need further clarified.