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

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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.