Expressional analysis of inwardly rectifying Kir4.1 channels in Noda epileptic rat (NER).

Abstract

The inwardly rectifying potassium channel subunit Kir4.1 is expressed in brain astrocytes and involved in spatial K(+) buffering, regulating neural activity. To explore the pathophysiological alterations of Kir4.1 channels in epileptic disorders, we analyzed interictal expressional levels of Kir4.1 in the Noda epileptic rat (NER), a hereditary animal model for generalized tonic-clonic (GTC) seizures. Western blot analysis showed that Kir4.1 expression in NERs was significantly reduced in the occipito-temporal cortical region and thalamus. However, the expression of Kir5.1, another Kir subunit mediating spatial K(+) buffering, remained unaltered in any brain regions examined. Immunohistochemical analysis revealed that Kir4.1 was primarily expressed in glial fibrillary acidic protein (GFAP)-positive astrocytes (somata) and foot processes clustered around neurons proved with anti-neuronal nuclear antigen (NeuN) antibody. In NERs, Kir4.1 expression in astrocytic processes was region-selectively diminished in the amygdaloid nuclei (i.e., medial amygdaloid nucleus and basomedial amygdaloid nucleus) while Kir4.1 expression in astrocytic somata was unchanged. Furthermore, the amygdala regions with reduced Kir4.1 expression showed a marked elevation of Fos protein expression following GTC seizures. The present results suggest that reduced activity of astrocytic Kir4.1 channels in the amygdala is involved in limbic hyperexcitability in NERs.

• Authors: Yuya Harada, Yuki Nagao, Saki Shimizu, Tadao Serikawa, Ryo Terada, Megumi Fujimoto, Aoi Okuda, Takahiro Mukai, Masashi Sasa, Yoshihisa Kurachi, Yukihiro Ohno
• Journal: Brain research (Brain Res) Vol. 1517 Pg. 141-9 (Jun 23 2013) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 23603404 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Glial Fibrillary Acidic Protein
• Kcnj10 (channel)
• Oncogene Proteins v-fos
• Potassium Channels, Inwardly Rectifying
• Phosphopyruvate Hydratase

Topics

• Amygdala (pathology)
• Animals
• Disease Models, Animal
• Epilepsy, Tonic-Clonic (genetics, metabolism, pathology)
• Gene Expression Regulation (genetics, physiology)
• Glial Fibrillary Acidic Protein (metabolism)
• Male
• Neuroglia (metabolism)
• Neurons (metabolism)
• Oncogene Proteins v-fos (metabolism)
• Phosphopyruvate Hydratase (metabolism)
• Potassium Channels, Inwardly Rectifying (genetics, metabolism)
• Rats
• Rats, Inbred WKY
• Rats, Mutant Strains