Astrocyte Ca2+ Signaling is Facilitated in an Scn1a+/- Mouse Model of Dravet Syndrome

Kouya Uchino; Yasuyoshi Tanaka; Wakana Ikezawa; Masanobu Deshimaru; Kaori Kubota; Takuya Watanabe; Shutaro Katsurabayashi; Katsunori Iwasaki; Shinichi Hirose

doi:10.1016/j.bbrc.2022.12.084

NeurosciencebioRxivMay 18, 2021

Astrocyte Ca2+ Signaling is Facilitated in an Scn1a+/- Mouse Model of Dravet Syndrome

Kouya Uchino iD, Yasuyoshi Tanaka iD, Wakana Ikezawa, Masanobu Deshimaru, Kaori Kubota iD, Takuya Watanabe iD, Shutaro Katsurabayashi iD, Katsunori Iwasaki, Shinichi Hirose iD

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Abstract

Dravet syndrome (DS) is an infantile-onset epileptic encephalopathy. More than 80% of DS patients have a heterozygous mutation in SCN1A, which encodes a subunit of the voltage-gated sodium channel, Nav1.1, in neurons. The roles played by astrocytes, the most abundant glial cell type in the brain, have been investigated in the pathogenesis of epilepsy; however, the specific involvement of astrocytes in DS has not been clarified. In this study, we evaluated Ca2+ signaling in astrocytes using genetically modified mice that have a loss-of-function mutation in Scn1a. We found that the slope of spontaneous Ca2+ spiking was increased without a change in amplitude in Scn1a+/- astrocytes. In addition, ATP-induced transient Ca2+ influx and the slope of Ca2+ spiking were also increased in Scn1a+/- astrocytes. These data indicate that perturbed Ca2+ dynamics in astrocytes may be involved in the pathogenesis of DS.