RGD Reference Report - Down-Regulation of Astrocytic Kir4.1 Channels during the Audiogenic Epileptogenesis in Leucine-Rich Glioma-Inactivated 1 (Lgi1) Mutant Rats. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Down-Regulation of Astrocytic Kir4.1 Channels during the Audiogenic Epileptogenesis in Leucine-Rich Glioma-Inactivated 1 (Lgi1) Mutant Rats.

Authors: Kinboshi, Masato  Shimizu, Saki  Mashimo, Tomoji  Serikawa, Tadao  Ito, Hidefumi  Ikeda, Akio  Takahashi, Ryosuke  Ohno, Yukihiro 
Citation: Kinboshi M, etal., Int J Mol Sci. 2019 Feb 26;20(5). pii: ijms20051013. doi: 10.3390/ijms20051013.
RGD ID: 14995940
Pubmed: (View Article at PubMed) PMID:30813600
DOI: Full-text: DOI:10.3390/ijms20051013

The dysfunction of astrocytic inwardly rectifying potassium (Kir) 4.1 channels, which mediate the spatial potassium-buffering function of astrocytes, is known to be involved in the development of epilepsy. Here, we analyzed the Kir4.1 expressional changes in Leucine-Rich Glioma-Inactivated 1 (Lgi1) mutant rats, which is a model of autosomal dominant lateral temporal lobe epilepsy in humans, to clarify the role of astrocytic Kir4.1 channels in Lgi1-related epileptogenesis. Priming acoustic stimulation (at postnatal day 16) conferred seizure susceptibility on Lgi1 mutant rats, which evoked audiogenic seizures with test stimulation at eight weeks. In the seizure-susceptible Lgi1 mutant rats (before test stimulation), astrocytic Kir4.1 expression was down-regulated region-specifically in the cerebral cortex, hippocampus, and amygdala. In addition, prophylactic treatments of Lgi1 mutant rats with valproic acid (VPA, 30 mg/kg and 200 mg/kg) for two weeks prevented both the development of seizure susceptibility and the down-regulation of Kir4.1 expression in astrocytes. The present study demonstrated for the first time that the astrocytic Kir4.1 expression was reduced in the Lgi1-related seizure model, suggesting that the down-regulation of Kir4.1 channels in astrocytes is involved in audiogenic epileptogenesis caused by Lgi1 mutation. In addition, VPA seemed to have a prophylactic effect on Lgi1-related seizures.

Annotation

Disease Annotations    

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

Genes (Rattus norvegicus)
Kcnj10  (potassium inwardly-rectifying channel, subfamily J, member 10)
Lgi1  (leucine-rich, glioma inactivated 1)
Lgi1m1Kyo  (leucine-rich, glioma inactivated 1; ENU induced mutant1, Kyo)
Lig1  (DNA ligase 1)

Genes (Mus musculus)
Kcnj10  (potassium inwardly-rectifying channel, subfamily J, member 10)
Lgi1  (leucine-rich repeat LGI family, member 1)
Lig1  (ligase I, DNA, ATP-dependent)

Genes (Homo sapiens)
KCNJ10  (potassium inwardly rectifying channel subfamily J member 10)
LGI1  (leucine rich glioma inactivated 1)
LIG1  (DNA ligase 1)

Strains
F344-Lgi1m1Kyo  (NA)
F344/NSlc  (NA)


Additional Information