Cavβ3 Contributes to the Maintenance of the Blood-Brain Barrier and Alleviates Symptoms of Experimental Autoimmune Encephalomyelitis.

Background: Tight control of cytoplasmic Ca concentration in endothelial cells is essential for the regulation of endothelial barrier function. Here, we investigated the role of Cavβ3, a subunit of voltage-gated Ca (Cav) channels, in modulating Ca signaling in brain microvascular endothelial cells (BMECs) and how this contributes to the integrity of the blood-brain barrier.

Methods: We investigated the function of Cavβ3 in BMECs by Ca imaging and Western blot, examined the endothelial barrier function in vitro and the integrity of the blood-brain barrier in vivo, and evaluated disease course after induction of experimental autoimmune encephalomyelitis in mice using Cavβ3 (Cavβ3-deficient) mice as controls.

Cavβ3 Regulates Ca Signaling and Insulin Expression in Pancreatic β-Cells in a Cell-Autonomous Manner.

Voltage-gated Ca (Cav) channels consist of a pore-forming Cavα1 subunit and auxiliary Cavα2-δ and Cavβ subunits. In fibroblasts, Cavβ3, independent of its role as a Cav subunit, reduces the sensitivity to low concentrations of inositol-1,4,5-trisphosphate (IP). Similarly, Cavβ3 could affect cytosolic calcium concentration ([Ca ]) in pancreatic β-cells.