title: Dysfunction of extrasynaptic GABAergic transmission in phospholipase C-related, but catalytically inactive protein 1 knockout mice is associated with an epilepsy phenotype.
abstract: Phospholipase C-related, but catalytically inactive protein (PRIP) was first identified as a novel inositol 1,4,5-triphosphate binding protein. The PRIP-1 subtype is expressed predominantly in the central nervous system and binds directly to the GABA type A receptor (GABA(A)-R) β-subunit and several other proteins involved in the trafficking of GABA(A)-Rs to the plasma membrane. We found that the PRIP-1 knockout mouse showed an epileptic phenotype, confirmed by electroencephalogram. These ictal seizures were completely suppressed by diazepam (DZP), but the interictal discharges could not be abolished. We studied the electrophysiological properties of GABAergic transmission in hippocampal CA1 pyramidal neurons, using a slice patch-clamp technique. There was no difference in the effect of up to 1 μM DZP on the amplitude and frequency of miniature inhibitory postsynaptic currents between PRIP-1 knockout neurons versus wild-type neurons. In contrast, the amplitude of the tonic GABA current in PRIP-1 knockout neurons was markedly reduced compared with that in wild-type neurons. Consequently, the effect of DZP on PRIP-1 knockout mice was reduced. Dysfunction of extrasynaptic GABAergic transmission probably is involved in the epileptic phenotype of PRIP-1 knockout mice.
authors: Department of Neuropsychiatry, Institute of Brain Science, Hirosaki University, Hirosaki, Japan.
authors: Gang
authors: G
authors: Zhu
authors: Shukuko
authors: S
authors: Yoshida
authors: Keisuke
authors: K
authors: Migita
authors: Junko
authors: J
authors: Yamada
authors: Fumiaki
authors: F
authors: Mori
authors: Masahiko
authors: M
authors: Tomiyama
authors: Koichi
authors: K
authors: Wakabayashi
authors: Takashi
authors: T
authors: Kanematsu
authors: Masato
authors: M
authors: Hirata
authors: Sunao
authors: S
authors: Kaneko
authors: Shinya
authors: S
authors: Ueno
authors: Motohiro
authors: M
authors: Okada
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D055162:Biocatalysis; D003975:Diazepam / Q000494:pharmacology; D004569:Electroencephalography; D004827:Epilepsy / Q000209:etiology*; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D011963:Receptors, GABA-A / Q000032:analysis; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C496391:Plcl1 protein, mouse; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D003975:Diazepam