Dysfunction of extrasynaptic GABAergic transmission in phospholipase C-related, but catalytically inactive protein 1 knockout mice is associated with an epilepsy phenotype

Gang Zhu, Shukuko Yoshida, Keisuke Migita, Junko Yamada, Fumiaki Mori, Masahiko Tomiyama, Koichi Wakabayashi, Takashi Kanematsu, Masato Hirata, Sunao Kaneko, Shinya Ueno, Motohiro Okada

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)520-528
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume340
Issue number3
DOIs
Publication statusPublished - Mar 2012

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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