The contribution of G protein-linked effector molecules and Gβγ subunits in the basic mechanisms of epilepsies

G蛋白连接效应分子和Gβγ亚基在癫痫基本机制中的贡献

基本信息

批准号：
12670925
负责人：
SHIMOYAMA Ichiro
金额：
$ 2.5万
依托单位：
CHIBA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670925/
关键词：
G protein effector G protein-gated inward rectifier potassium channel βadrenergic receptor kinase kindling temporal lobe epilepsy epilepsy Gβγ subunits G蛋白質 βγサブユットてんかんキンドリング GIRK 細胞内情報伝達

项目摘要

Several studies have demonstrated the involvement of βγ subunits of trimeric G protein (Gβγ) in the neural transduction system. G protein-gated inward rectifier potassium channel (GIRK) and (β-adrenergic receptor kinase (βARK) is regulated by Gβγ subunits and modulates functions of G protein-coupled ion channels and receptors. It is reported that neural transmission via such effectors plays an important role in the molecular basis of epilepsy. The purpose of the present research was to clarify the contribution of Gβγ subunits and effector molecules in the basic mechanisms of epilepsy. We examined the alteration in expression level of GIRK, βARK, Gβ and Gγ subunits in the resected hippocampus of a patient with refractory temporal lobe epilepsy (TLE) and amygdaloid kindling model in rats.In the kindling studies, remarkable increase of immunoreactivities in expression level of βARK1 , βARK2 and Gβ1 were seen in the hippocampus at 24 h after the last seizure in the partially-kindled (PK) and fully-kindled (FK) groups. The expression levels of Gp2, GIRK2 and GY3 were also increased in the FK group. A greater increase in expression level of Gβ1, GIRK2 and Gγ3 were observed in spiking areas than in non-spiking areas. In the resected hippocampus of TLE, βARK1 level was remarkably increased in non-spiking areas.The present results provide evidence that the alteration in the expression level of βARK1 and Gβ1 may be related to the acquisition process of epileptogenesis and induction of generalized seizure. However, since the increase in βARK1 was remarkable in the non spiking areas in TLE, such alteration might reflect the compensatory inhibitory mechanisms to the epileptic hyperexcitability in the epileptogeneic zone.

几项研究表明，三聚体G蛋白（Gβγ）的βγ亚基参与神经传导系统。 G蛋白接收的内向整流钾通道（GIRK）和（β-肾上腺素能受体激酶（βARK）受Gβγ亚基调节，并调节G蛋白偶联离子通道和受体的功能。据报道，通过这种效应在epilepsy的分子基础上通过这种效应在epilepsy的贡献中起着重要作用。在发作的基本机制中，我们检查了girk，βark，gβ和Gγ亚基的表达水平的改变在部分癫痫发作（PK）中，在24小时内观察到Gβ1，而GP2的表达水平，GIRK2和GY3的表达水平也比GP2的表达增加了。在切除的TLE海马中，非加速区域的βARK1水平明显增加。目前的结果提供了证据，表明βARK1和Gβ1的表达水平的改变可能与癫痫发生和广义性癫痫的诱导过程有关。但是，由于在TLE的非尖峰区域中βARK1的增加是显着的，因此这种变化可能反映了癫痫症中癫痫过度过度抗性性的补偿性抑制机制。