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