The major findings of the present study are that both genetic deletion in vivo and pharmacological blockade of KCa3.1 in vitro inhibit upregulation of astrogliosis marker GFAP, which is accompanied by decreased ER stress markers GRP78 and eIF-2α, in both OGD-induced astrocytes and in the pMCAO mouse model of ischemic stroke. Here, HSPA5 is linked to ischemic stroke.