Endothelial calcium dynamics, connexin channels and blood–brain barrier function

• Published in: Progress in neurobiology Vol. 108; pp. 1 - 20
• Main Authors: De Bock, Marijke, Wang, Nan, Decrock, Elke, Bol, Mélissa, Gadicherla, Ashish K., Culot, Maxime, Cecchelli, Romeo, Bultynck, Geert, Leybaert, Luc
• Format: Journal Article
• Language: English
• Published: England Elsevier 01.09.2013
• Subjects: Adenosine Triphosphate - physiology; Animals; blood-brain barrier; Blood-Brain Barrier - physiology; brain; calcium; Calcium - metabolism; Calcium - physiology; calcium signaling; Calcium Signaling - physiology; Connexins - metabolism; cytoskeletal proteins; Cytoskeletal Proteins - metabolism; cytoskeleton; edema; endothelial cells; Endothelium - metabolism; Humans; inflammation; Life Sciences; Neuroglia - physiology; neuropathology; permeability; Tight Junctions - physiology; toxins; BCEC; PAR; Connexin channels; BBB; nuclear factor κB; MLC; Ca(2+)/calmodulin-dependent kinase II; phospholipase A2; vasodilator-stimulated phosphoprotein; calmodulin; intercellular adhesion molecule 1; myosin light chain kinase; CaM; ICAM1; TRP; myosin light chain; G-protein coupled receptor; Cx; NADPH oxidase; arachidonate-regulated Ca(2+) entry channels; Endothelial permeability; MDCK; nitric oxide synthase; connexin; inositol 1,4,5-trisphosphate; NFκB; PLA2; bradykinin; PKC; MAPK; ER; MMP; p/sGC; ARC; NOS; ZO; NMDA-R; ROS; GPCR; N-methyl-d-aspartate-sensitive receptor; inositol 1,4,5-trisphosphate receptor; nicotinamide adenine dinucleotide phosphate oxidase; cyclic guanosine monophosphate; PLC; BK; cGMP; CRAC; Blood–brain barrier; mitogen-activated protein kinase; stromal interaction molecule; particulate/soluble guanylyl cyclase; reactive oxygen species; Ca(2+) release-activated channels; protein kinase C; InsP; VASP; phospholipase C; MLCK; STIM; matrix-metalloproteinase; VEGF; InsPR; Ca(2+) dynamics; Madine–Darby canine kidney cells; transient receptor potential; CaMKII; vascular endothelial growth factor; bovine brain capillary endothelial cells; protease-activated receptor; endoplasmic reticulum; zonula occludens; 5-trisphosphate receptor; blood–brain barrier; inositol 1; 5-trisphosphate
• ISSN: 0301-0082; 1873-5118; 1873-5118
• DOI: 10.1016/j.pneurobio.2013.06.001

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.