Membrane Hyperpolarization Induced by Endoplasmic Reticulum Stress Facilitates Ca2+ Influx to Regulate Cell Cycle Progression in Brain Capillary Endothelial Cells

Abstract.: Upregulation of the Kir2.1 channel during endoplasmic reticulum (ER) stress in t-BBEC117, an immortalized bovine brain endothelial cell line, caused a sustained increase in intracellular Ca2+ concentration ([Ca2+]i) and a facilitation of cell death. Expressions of Ca2+ influx channels (TRPC, Orai1, STIM1) were unchanged by ER stress. The ER stress–induced [Ca2+]i increase was mainly attributed to the deeper resting membrane potential due to Kir2.1 upregulation. ER stress arrested at the G2/M phase and it was attenuated by an inhibitor of Kir2.1. These results indicate that Kir2.1 upregulation by ER stress facilitates cell death via regulation of cell cycle progression in t-BBEC117. Keywords:: brain capillary endothelial cell, store operated calcium entry, endoplasmic reticulum stress