title: Ion transporters in brain endothelial cells that contribute to formation of brain interstitial fluid.
abstract: Ions and water transported across the endothelium lining the blood–brain barrier contribute to the fluid secreted into the brain and are important in maintaining appropriate volume and ionic composition of brain interstitial fluid. Changes in this secretion process may occur after stroke. The present study identifies at transcript and protein level ion transporters involved in the movement of key ions and examines how levels of certain of these alter following oxidative stress. Immunohistochemistry provides evidence for Cl−/HCO3− exchanger, AE2, and Na+, HCO3− cotransporters, NBCe1 and NBCn1, on brain microvessels. mRNA analysis by RT-PCR reveals expression of these transporters in cultured rat brain microvascular endothelial cells (both primary and immortalized GPNT cells) and also Na+/H+ exchangers, NHE1 (primary and immortalized) and NHE2 (primary cells only). Knock-down using siRNA in immortalized GPNT cells identifies AE2 as responsible for much of the Cl−/HCO3− exchange following extracellular chloride removal and NHE1 as the transporter that accounts for most of the Na+/H+ exchange following intracellular acidification. Transcript levels of both AE2 and NHE1 are increased following hypoxia/reoxygenation. Further work is now required to determine the localization of the bicarbonate transporters to luminal or abluminal membranes of the endothelial cells as well as to identify and localize additional transport mechanisms that must exist for K+ and Cl−.
authors.forename: Ruth
authors.initials: R
authors.lastname: Mokgokong
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wang
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Taylor
authors.forename: Margery A
authors.initials: MA
authors.lastname: Barrand
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Hladky
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000166:cytology / Q000378:metabolism*; D002199:Capillary Permeability; D002460:Cell Line; D002478:Cells, Cultured; D027963:Chloride-Bicarbonate Antiporters / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D045604:Extracellular Fluid / Q000378:metabolism*; D017136:Ion Transport; D055806:Microvessels / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D027982:Sodium-Bicarbonate Symporters / Q000235:genetics / Q000378:metabolism*; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism*
chemical_list: D027963:Chloride-Bicarbonate Antiporters; D012333:RNA, Messenger; C422004:Slc4a4 protein, rat; C498902:Slc4a7 protein, rat; C452850:Slc9a1 protein, rat; D027982:Sodium-Bicarbonate Symporters; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers
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