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

Marijke de Bock , Nan Wang , Elke Decrock , Mélissa Bol , Ashish Gadicherla , Maxime Culot (1) , Roméo Cecchelli (1) , Geert Bultynck , Luc Leybaert

1 LBHE - Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique

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.

Keywords: 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.

Domains: Life Sciences [q-bio]

Marijke de Bock, Nan Wang, Elke Decrock, Mélissa Bol, Ashish Gadicherla, et al.. Endothelial calcium dynamics, connexin channels and blood–brain barrier function. Progress in Neurobiology, 2013, 108, pp.1-20. ⟨10.1016/j.pneurobio.2013.06.001⟩. ⟨hal-02515498⟩