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

已有研究表明，三聚体G蛋白（Gβγ）βγ亚基参与神经转导系统。G蛋白门控内向整流钾通道（GIRK）和β-肾上腺素能受体激酶（β方舟激酶）受Gβγ亚基的调节，并调节G蛋白偶联离子通道和受体的功能。据报道，通过这些效应器的神经传递在癫痫的分子基础中起着重要作用。本研究旨在阐明Gβγ亚基及其效应分子在癫痫发病机制中的作用。本研究观察了难治性颞叶癫痫（TLE）大鼠海马组织中GIRK、β方舟、Gβ和Gγ亚单位表达水平的变化。末次癫痫发作后24 h，部分点燃（PK）组和完全点燃（FK）组海马可见β ARK 2和Gβ1。FK组Gp 2、GIRK 2和GY 3的表达水平也升高。GIRK 2、Gβ1和Gγ3在加标区的表达水平明显高于非加标区。在TLE患者切除的海马中，β ARK 1在非棘波区的表达明显增加，提示β ARK 1和Gβ1的表达变化可能与癫痫发生的获得过程和全身性发作的诱发有关。但由于β ARK 1在TLE非峰电位区的表达明显增加，这种变化可能反映了致痫区对癫痫高兴奋性的代偿性抑制机制。

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.