Polarized hemichannel opening of pannexin 1/connexin 43 contributes to dysregulation of transport function in blood-brain barrier endothelial cells

Masanori Tachikawa, Koji Murakami, Ryo Akaogi, Shin ichi Akanuma, Tetsuya Terasaki, Ken ichi Hosoya

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Dysregulation of blood-brain barrier (BBB) transport exacerbates brain damage in acute ischemic stroke. Here, we aimed to investigate the mechanism of this BBB transport dysregulation by studying the localization and function of pannexin (Px) and connexin (Cx) hemichannels in blood-brain barrier endothelial cells of rat (TR-BBB13 cells) and human (hCMEC/D3 cells) under acute ischemic stroke-mimicking oxygen/glucose deprivation (OGD) and extracellular Ca2+ ([Ca2+]e)-free conditions. TR-BBB13 cells showed increased uptake of hemichannel-permeable sulforhodamine 101, and this increase was markedly inhibited by carbenoxolone, a hemichannel inhibitor. Transcripts of Px1 and Cx43 were detected in TR-BBB13 cells and freshly isolated brain microvascular endothelial cells. The basal compartment-to-cell uptake of hemichannel-permeable propidium iodide was selectively enhanced in hCMEC/D3 cells under [Ca2+]e-free conditions in the basal Transwell chamber. Immunohistochemical analysis revealed the predominant localization of Cx43 on the lateral membranes of hCMEC/D3 cells. [3H]Taurine uptake by hCMEC/D3 cells was significantly reduced in the absence of [Ca2+]e. Functional knock-down of Px1 and Cx43 with mimetic peptides significantly inhibited the increase of ATP release from hCMEC/D3 cells under [Ca2+]e-free conditions. These results suggest that polarized Px1/Cx43 hemichannel opening in brain capillary endothelial cells under acute ischemic stroke-mimicking conditions contributes to dysregulation of BBB transport function, resulting in release of intracellular taurine and ATP.

Original languageEnglish
Article number104600
JournalNeurochemistry International
Volume132
DOIs
Publication statusPublished - 2020 Jan

Keywords

  • Acute stroke
  • Blood-brain barrier
  • Connexin 43
  • Hemichannel
  • Pannexin 1

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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