Astrocyte Ca2+ signaling is facilitated in Scn1a+/− mouse model of Dravet syndrome

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. •Ca2+ spiking was significantly faster in astrocytes cultured from Scn1a+/− mice.•ATP-induced Ca2+ spiking was also significant in astrocytes cultured from Scn1a+/− mice.•Restoring Ca2+ signaling in astrocytes would lead to the development of novel therapies for epilepsy.