摘要
目的 :探讨G蛋白偶联内向整流钾通道 (GIRK)在海人酸诱导慢性颞叶癫痫大鼠海马内的表达变化及其在癫痫中的作用。方法 :采用海人酸颞叶癫痫模型 ,运用原位杂交、免疫细胞化学检测海马齿状回、CA1、CA3区GIRK1、2mRNA和蛋白表达 ;Westernblotting检测海马整体GIRK1、2蛋白变化。结果 :GIRK1、2mRNA和蛋白在大鼠海马内分布广泛 ;慢性颞叶癫痫海马DG区GIRK2mRNA和蛋白表达增高有显著差异 (P <0 0 1) ;GIRK1mRNA在海马DG区表达有差异 (P <0 0 5 ) ;Westernblotting检测海马GIRK1、2未有明显变化。结论 :GIRK1、2在慢性癫痫大鼠海马内的表达增高 ,特别在齿状回 ,提示是机体对神经元网络过度兴奋的代偿或适应性反应 ;其合成增加将降低神经元的兴奋性 ,阻止海马内过度兴奋的扩散 (DG -CA3-CA1)。
AIM: G protein-coupled inwardly rectifier potassium (GIRK) channel are distributed widely in mammalian brain. In CNS, GIRK 1/2 seems to be the predominant heterotetramers which play a pivot role in the regulation of the excitability of neurons and may contribute to the resting potential by leading to a hyperpolarization of membrane potential and reduction of the action potential frequency. In the context, the Weaver mouse is the first neurological abnormality directly linked to a genetic point mutation in the GIRK2 protein which includes spontaneous seizure. GIRK2 knock out mice showed normal development but more susceptible than normal mice to seizure induced by GABA antagonist. Here, we report that the mRNA and protein expression of GIRK subunit 2 is altered in kainic acid(KA)-induced epileptic rat hippocampus. METHODS: Rats were injected with kainate 14 mg/kg intraperitoneally to establish an acute and chronic temporal lobe epilepsy model. At chronic spontaneous seizure stage, by using of in situ hybridization, immunocytochemistry and Western blotting, the GIRK 1,2 mRNA and protein were analyzed quantitatively in the dentate gyreus, CA1, CA3 regions of hippocampus. RESULTS: GIRK1,2 mRNA and proteins were expressed abundantly in all regions of hippocampus. KA induced seizures and caused a significant increase in GIRK2 mRNA abundance and immunoreacitivity; only GIRK1 mRNA was increased significantly, but no difference was found by Western blotting protocol. CONCLUSION: GIRK1,2 mRNA and protein expression in the hippocampus of epileptic rat brain is up-regulated, which may be an adaptive response to over-excitability of neuron networks and prevent the over-excitability spread in hippocampus (DG-CA3-CA1). [
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2004年第10期1882-1886,共5页
Chinese Journal of Pathophysiology
基金
高等学校博士学科点专项基金资助项目 (No .2 0 0 30 5 330 4 2 )
高等学校优秀青年教师学科研奖励计划(No .2 0 0 1- 182 )
关键词
癫痫
颞叶
离子通道
海马
GTP结合蛋白质类
Epilepsy, temporal lobe
Ion channels
Hippocampus
GTP-binding proteins
