Kv7 CHANNELS ACTIVATION REDUCES BRAIN ENDOTHELIAL CELLS PERMEABILITY AND PREVENTS KAINIC ACID INDUCED BLOOD BRAIN BARRIER DAMAGE

In this study, using morphological and functional approaches, we evaluated the expression and role in the BBB of Kv7 channels, a family of voltage-gated potassium channels including five members (Kv7.1-5) that play a major role in the regulation of cell excitability and transmembrane flux of potassium ions. Immunofluorescence experiments showed that Kv7.1, Kv7.4 and Kv7.5 were expressed in rat brain microvessels (BMVs), as well as well as brain primary- and clonal (BEND-3) endothelial cells (ECs). Kv7.5 localized at the cell-to cell junction sites, whereas Kv7.4 was also found in pericytes. The Kv7 activator retigabine increased trans-endothelial electrical resistance (TEER) in both primary ECs and BEND-3 cells; moreover, retigabine reduced paracellular dextran flux in BEND-3 cells. These effects were prevented by the selective Kv7 blocker XE-991. Exposure to retigabine also hyperpolarized cell membrane and increased tight junctions (TJs) integrity in BEND-3 cells. BMVs from rats treated with kainic acid (KA) showed a disruption of TJs and a selective reduction of Kv7.5 expression. In BEND-3 cells, retigabine prevented the increase of cell permeability and the reduction of TJs integrity induced by KA. Overall, these findings demonstrate that Kv7 channels are expressed in the BBB, where they modulate barrier properties both in physiological and pathological conditions.PMID:38284124 | DOI:10.1152/ajpcell.00709.2023
Source: Am J Physiol Cell Ph... - Category: Cytology Authors: Source Type: research