Author/Authors :
Harada، Yuya نويسنده Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan , , Nagao، Yuki نويسنده Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan , , Mukai، Takahiro نويسنده , , Shimizu، Saki نويسنده Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan , , Tokudome، Kentaro نويسنده Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan , , Kunisawa، Naofumi نويسنده Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan , , Serikawa، Tadao نويسنده Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan , , Sasa، Masashi نويسنده Nagisa Clinic, Hirakata, Osaka, Japan , , Ohno، Yukihiro نويسنده Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan ,
Abstract :
The inwardly rectifying potassium channel subunit Kir4.1 is specifically expressed in astrocytes, which mediates spatial K+ buffering and is implicated in the pathogenesis of convulsive epileptic disorders (ie, generalized tonic-clonic (GTC) and temporal lobe seizures). This study aimed to explore the pathophysiological role of Kir4.1 channels in modulating absence seizure incidence, using a spontaneously epileptic animal model. Groggy rats, a rat model of human absence seizures, and Slc:Wistar (control) rats, were used in this study. Cortical and hippocampal EEG were recorded to confirm the seizure incidence in Groggy rats. The expression levels of Kir subunits (ie, Kir4.1, Kir5.1 and Kir2.1) in ten brain regions were analyzed by Western blotting. Groggy rats showed a high incidence (ca. 350 seconds total duration/15 minutes observation period) of absence-like seizures, which were characterized by a sudden immobile posture and synchronously-associated spike and wave discharges. However, Western blot analysis revealed that Kir4.1 expression in Groggy rats was not significantly different from that of control rats in any of the brain regions examined (eg, cerebral cortex, striatum, hippocampus, diencephalon, midbrain, pons/medulla oblongata and cerebellum). In addition, expressional levels of Kir5.1 and Kir2.1, which are also expressed in astrocytes, were unaltered in Groggy rats. The present results suggest that unlike GTC and temporal lobe seizures, pathophysiological alterations (eg, dysfunction and/or expressional changes) of Kir4.1 are not linked to non-convulsive absence seizures.
