Endothelial calcium dynamics, connexin channels and blood–brain barrier function
Résumé
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.
Mots clés
blood–brain barrier
bovine brain capillary endothelial cells
bradykinin
cGMP
calmodulin
connexin
cyclic guanosine monophosphate
endoplasmic reticulum
inositol 1
5-trisphosphate
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.