Astrocytes in Atp1a2-deficient heterozygous mice exhibit hyperactivity after induction of cortical spreading...

The ATP1A2 coding α2 subunit of Na,K-ATPase, which is predominantly located in astrocytes, is a causative gene of familial hemiplegic migraine type 2 (FHM2). FHM2 model mice (Atp1a2^tmCKwk/+ ) are susceptible to cortical spreading depression (CSD), which is profoundly related to migraine aura and headache. However, astrocytic properties during CSD have not been examined in FHM2 model mice. Using Atp1a2^tmCKwk/+ crossed with transgenic mice expressing G-CaMP7 in cortical neurons and astrocytes (Atp1a2^+/- ), we analyzed the changes in Ca²⁺ concentrations during CSD. The propagation speed of Ca²⁺ waves and the percentages of astrocytes with elevated Ca²⁺ concentrations in Atp1a2^+/- were higher than those in wild-type mice. Increased percentages of astrocytes with elevated Ca²⁺ concentrations in Atp1a2^+/- may contribute to FHM2 pathophysiology.