Calcium Modulation of Adherens and Tight Junction Function

Abstract

This review deals with the role of calcium in endothelial cell junctions of the blood-brain barrier (BBB). Calcium is critical for adherens junction function, but it appears that calcium is also important in regulating tight junction function necessary for the barrier characteristics of cerebral microvessels. The BBB is critical for brain homeostasis and is located at the cerebral microvessel endothelial cells. These endothelial cells maintain their barrier characteristics via cell-cell contacts made up of adherens and tight junctions. Adherens junctions are calcium dependent; recent evidence suggests that calcium also affects tight junctions. After stroke, there is a disruption of the BBB. Interfering with calcium flux under hypoxic conditions can prevent BBB breakdown. Calcium may alter BBB junction integrity by a number of different signal transduction cascades, as well as via direct interaction of calcium ions with junction proteins. It remains to be determined whether clinical use of calcium channel antagonists is a viable means to reduce BBB disruption after stroke. With the widespread use of calcium channel blockers as clinical treatments for hypertension, which is a risk factor for stroke, the exact role of calcium in modulating BBB integrity needs to be elucidated.