Astrocyte Ca2+ Signaling is Facilitated in an 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, Nav 1.1 , 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 Ca 2+ signaling in astrocytes using genetically modified mice that have a loss-of-function mutation in Scn1a . We found that the slope of spontaneous Ca 2+ spiking was increased without a change in amplitude in Scn1a +/− astrocytes. In addition, ATP-induced transient Ca 2+ influx and the slope of Ca 2+ spiking were also increased in Scn1a +/− astrocytes. These data indicate that perturbed Ca 2+ dynamics in astrocytes may be involved in the pathogenesis of DS.