Up-regulation of Kir2.1 by ER stress facilitates cell death of brain capillary endothelial cells

► We found that application of endoplasmic reticulum (ER) stress with tunicamycin to brain capillary endothelial cells (BCECs) induced cell death. ► The ER stress facilitated the expression of inward rectifier K+ channel (Kir2.1) and induced sustained membrane hyperpolarization. ► The membrane hyperpolarization induced sustained Ca2+ entry through voltage-independent nonspecific cation channels and consequently facilitated cell death. ► The Kir2.1 up-regulation by ER stress is, at least in part, responsible for cell death of BCECs under pathological conditions.