title: Up-regulation of K(ir)2.1 by ER stress facilitates cell death of brain capillary endothelial cells.
abstract: Brain capillary endothelial cells (BCECs) form blood brain barrier (BBB) to maintain brain homeostasis. Cell turnover of BCECs by the balance of cell proliferation and cell death is critical for maintaining the integrity of BBB. Here we found that stimuli with tunicamycin, endoplasmic reticulum (ER) stress inducer, up-regulated inward rectifier K(+) channel (K(ir)2.1) and facilitated cell death in t-BBEC117, a cell line derived from bovine BCECs. The activation of K(ir) channels contributed to the establishment of deeply negative resting membrane potential in t-BBEC117. The deep resting membrane potential increased the resting intracellular Ca(2+) concentration due to Ca(2+) influx through non-selective cation channels and thereby partly but significantly regulated cell death in t-BBEC117. The present results suggest that the up-regulation of K(ir)2.1 is, at least in part, responsible for cell death/cell turnover of BCECs induced by a variety of cellular stresses, particularly ER stress, under pathological conditions.
authors: Department of Molecular & Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
authors: Hiroaki
authors: H
authors: Kito
authors: Daiju
authors: D
authors: Yamazaki
authors: Susumu
authors: S
authors: Ohya
authors: Hisao
authors: H
authors: Yamamura
authors: Kiyofumi
authors: K
authors: Asai
authors: Yuji
authors: Y
authors: Imaizumi
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply*; D002196:Capillaries; D002417:Cattle; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000096:biosynthesis*; D013312:Stress, Physiological; D014415:Tunicamycin / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: C489461:Kir2.1 channel; D024661:Potassium Channels, Inwardly Rectifying; D014415:Tunicamycin