title: [GABA(A) receptor trafficking and epilepsy].
abstract: Recent studies clarified a dynamic regulation of the intracellular trafficking of GABA(A) receptors and its involvement in the pathophysiology of epilepsy. GABA(A) synaptic inhibition decreased in the hippocampal CA1 area of patients with intractable temporal lobe epilepsy (TLE). The reduction of GABAergic inhibition was accompanied by a decrease in the expression of gephyrin, a scaffolding protein, and GABA(A) receptor gamma2 subunit. These findings indicate that the reduction of gephyrin impairs the clustering and fixation of GABA(A) receptors in postsynaptic membranes, leading to a decrease in number of GABA(A) receptor subunits and GABA(A) synaptic inhibition. In contrast, the GABA(A) synaptic inhibition was lastingly potentiated in the dentate gyrus of kindled animals and the expression of GABA(A) receptor subunits(especially alpha2) was significantly increased in TLE patients. It is plausible that the potentiation of dentate GABAergic inhibition counteracts a hyperexcitability of granule cells as a defense mechanism in epilepsy. In status epilepticus, furthermore, the hippocampal GABA(A) receptor beta3 subunits were significantly disphosphorylated, resulting in a facilitation of the endocytosis of GABA(A) receptors and reduced benzodiazepine sensitivity.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Maru
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ura
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D004827:Epilepsy / Q000235:genetics* / Q000378:metabolism; D005089:Exocytosis; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000502:physiology; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D011963:Receptors, GABA-A; D017981:Receptors, Neurotransmitter; C073441:gephyrin; C069474:glutamine receptor