The role of ion channels expressed in cerebral endothelial cells in the functional integrity of the blood-brain barrier

Abstract

All anatomical elements contributing to the blood-brain barrier (BBB) play a crucial role in maintaining the permeability and CNS homeostasis under physiological/pathological conditions. These elements are endothelial cells, pericytes, astroglia, and neurons that are known as a neurovascular unit (NVU). Being the integral system, NVU contributes to the regulation of neuroplasticity, neurogenesis, intercellular communications and permeability of BBB. Brain capillary endothelial cells (BCEC) are the very important part of NVU. In this review, we discuss the critical role of BCEC ion channels in BBB structural and functional integrity. In last decades, much attention has been paid to the expression of tight junctions and adherence junctions in BCEC whereas less number of studies was focused on the expression and functioning of ion channels in BCEC, however, there is growing evidence supporting their important role in the regulation of NVU/BBB functions. In general, electrophysiological properties of BCEC depend on the expression of various ion channels whose activity, presumably, coordinates intercellular communication within the NVU. Particularly, we focus on BCEC ion channels-dependent mechanisms of NVU functioning, arteriole smooth muscle cells dynamic modulation, and changes in the regional cerebral blood flow. We put special attention on ligand-gated ion channels, store-operated calcium channels, TRP ion channels, calcium-activated, voltage-gated potassium channels in BCEC. Understanding the role of ion channel signaling in the control of cerebral blood flow will helps to reveal the potential therapeutic targets to recover the NVU/BBB functional integrity in different pathological conditions (ischemia, neuroinflammation, neurodegeneration) both in vivo and in vitro BBB models.