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bioRxiv · 10.1101/2021.05.18.444602

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

Uchino, K.·Ikezawa, W.·Tanaka, Y.·Deshimaru, M.·Kubota, K.·Watanabe, T.·Katsurabayashi, S.·Iwasaki, K.·Hirose, S.
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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.

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Uchino, K., Ikezawa, W., Tanaka, Y., Deshimaru, M., Kubota, K., Watanabe, T., Katsurabayashi, S., Iwasaki, K., Hirose, S.. 2021-05-18. Astrocyte Ca2+ Signaling is Facilitated in an Scn1a+/- Mouse Model of Dravet Syndrome. https://doi.org/10.1101/2021.05.18.444602

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