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.