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

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, 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 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.

Keywords: Astrocyte; Ca(2+) spiking; Dravet syndrome; Epilepsy.