ATP受体通道激活增加谷氨酸对海马神经元的损伤

ATP channel activation increases the vulnerability of Hippocampal neurons to glutamate

目的探讨胞外三磷酸腺苷(adenosine triphosphate,ATP)、谷氨酸(glutamate,Glu)对海马神经元的作用及其机制。方法孕18d胎鼠取海马神经元原代培养,分为正常对照组、ATP组、Glu组、ATP+Glu组。台盼蓝计数检测细胞存活率,全细胞电压钳记录细胞膜电流情况。结果台盼蓝计数显示,ATP(100μmol/L)、Glu(100μmol/L)以及ATP+Glu(100μmol/L+100μmol/L)分别处理后海马神经元死亡率依次增加。全细胞电压钳显示,单独给予100μmol/L ATP没有明显的电流产生,100μmol/L Glu可诱导较大的内向电流,二者共同作用增加了电流大小。结论 ATP受体通道激活增加谷氨酸对海马神经元的损伤及谷氨酸受体通道的活性。在阿尔兹海默病等与兴奋毒性有关的紊乱发病机制中可能起重要作用。

Objective To investigate extracellular adenosine triphospbate （ ATP）, glutamate （Gin） on hippocampal neurons in rats. Methods Primary cultured hippocampal neurons taken from 18 days gestation fetuses were divided into normal control group, ATP group, Glu group, ATP ＋ Glu group. Trypan blue exclusion testing cell viability, whole-cell volt- age-clamp recording membrane currents. Results Trypan blue display mortality of hippocampal neurons increased sequen- tially after ATP（ 100μmol/L） ,Glu（ 100μmol/L） and ATP ＋ Glu（ 100μmol/L ＋ 100μmol/L） were treated. Whole-cell volt- age clamp showed no significant current generation given 100μmol/L ATP alone, 100μmol/L Glu can induce large inward currents,both increases the current size. Conclusion ATP increased activation of glutamate receptor channels in hipp- ocampal neuronal damage and glutamate receptor channel activity. Excitotoxicity associated with disorders such as Alzhei- mer＇s disease pathogenesis may play an important role.