title: Endothelial calcium dynamics, connexin channels and blood-brain barrier function.
abstract: Situated between the circulation and the brain, the blood-brain barrier (BBB) protects the brain from circulating toxins while securing a specialized environment for neuro-glial signaling. BBB capillary endothelial cells exhibit low transcytotic activity and a tight, junctional network that, aided by the cytoskeleton, restricts paracellular permeability. The latter is subject of extensive research as it relates to neuropathology, edema and inflammation. A key determinant in regulating paracellular permeability is the endothelial cytoplasmic Ca(2+) concentration ([Ca(2+)]i) that affects junctional and cytoskeletal proteins. Ca(2+) signals are not one-time events restricted to a single cell but often appear as oscillatory [Ca(2+)]i changes that may propagate between cells as intercellular Ca(2+) waves. The effect of Ca(2+) oscillations/waves on BBB function is largely unknown and we here review current evidence on how [Ca(2+)]i dynamics influence BBB permeability.
authors.affiliation: Dept. of Basic Medical Sciences, Ghent University, Ghent, Belgium. marijke.debock@ugent.be
authors.forename: Marijke
authors.initials: M
authors.lastname: De Bock
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Elke
authors.initials: E
authors.lastname: Decrock
authors.forename: Mélissa
authors.initials: M
authors.lastname: Bol
authors.forename: Ashish K
authors.initials: AK
authors.lastname: Gadicherla
authors.forename: Maxime
authors.initials: M
authors.lastname: Culot
authors.forename: Romeo
authors.initials: R
authors.lastname: Cecchelli
authors.forename: Geert
authors.initials: G
authors.lastname: Bultynck
authors.forename: Luc
authors.initials: L
authors.lastname: Leybaert
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D002118:Calcium / Q000378:metabolism* / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D017630:Connexins / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism*; D006801:Humans; D009457:Neuroglia / Q000502:physiology; D019108:Tight Junctions / Q000502:physiology
chemical_list: D017630:Connexins; D003598:Cytoskeletal Proteins; D000255:Adenosine Triphosphate; D002118:Calcium
keywords: ARC; BBB; BCEC; BK; Blood–brain barrier; CRAC; Ca(2+) dynamics; Ca(2+) release-activated channels; Ca(2+)/calmodulin-dependent kinase II; CaM; CaMKII; Connexin channels; Cx; ER; Endothelial permeability; G-protein coupled receptor; GPCR; ICAM1; InsP(3); InsP(3)R; MAPK; MDCK; MLC; MLCK; MMP; Madine–Darby canine kidney cells; N-methyl-d-aspartate-sensitive receptor; NADPH oxidase; NFκB; NMDA-R; NOS; PAR; PKC; PLA2; PLC; ROS; STIM; TRP; VASP; VEGF; ZO; arachidonate-regulated Ca(2+) entry channels; blood–brain barrier; bovine brain capillary endothelial cells; bradykinin; cGMP; calmodulin; connexin; cyclic guanosine monophosphate; endoplasmic reticulum; inositol 1,4,5-trisphosphate; inositol 1,4,5-trisphosphate receptor; intercellular adhesion molecule 1; matrix-metalloproteinase; mitogen-activated protein kinase; myosin light chain; myosin light chain kinase; nicotinamide adenine dinucleotide phosphate oxidase; nitric oxide synthase; nuclear factor κB; p/sGC; particulate/soluble guanylyl cyclase; phospholipase A2; phospholipase C; protease-activated receptor; protein kinase C; reactive oxygen species; stromal interaction molecule; transient receptor potential; vascular endothelial growth factor; vasodilator-stimulated phosphoprotein; zonula occludens