Affordable Access

deepdyve-link
Publisher Website

Contribution of pannexin 1 and connexin 43 hemichannels to extracellular calcium-dependent transport dynamics in human blood-brain barrier endothelial cells.

Authors
  • Kaneko, Yosuke
  • Tachikawa, Masanori
  • Akaogi, Ryo
  • Fujimoto, Kazuhisa
  • Ishibashi, Megumi
  • Uchida, Yasuo
  • Pierre-Olivier Couraud
  • Ohtsuki, Sumio
  • Hosoya, Ken-ichi
  • Terasaki, Tetsuya
Type
Published Article
Journal
Bulletin de l'Académie nationale de médecine
Publication Date
April 2015
Volume
353
Issue
1
Pages
192–200
Identifiers
DOI: 10.1124/jpet.114.220210
PMID: 25670633
Source
USPC - SET - SVS
License
Unknown

Abstract

Dysregulation of blood-brain barrier (BBB) transport function is thought to exacerbate neuronal damage in acute ischemic stroke. The purpose of this study was to clarify the characteristics of pannexin (Px) and/or connexin (Cx) hemichannel(s)-mediated transport of organic anions and cations in human BBB endothelial cell line hCMEC/D3 and to identify inhibitors of hemichannel opening in hCMEC/D3 cells in the absence of extracellular Ca(2+), a condition mimicking acute ischemic stroke. In the absence of extracellular Ca(2+), the cells showed increased uptake and efflux transport of organic ionic fluorescent dyes. Classic hemichannel inhibitors markedly inhibited the enhanced uptake and efflux. Quantitative targeted absolute proteomics confirmed Px1 and Cx43 protein expression in plasma membrane of hCMEC/D3 cells. Knockdown of Px1 and Cx43 with the small interfering RNAs significantly inhibited the enhanced uptake and efflux of organic anionic and cationic fluorescent dyes. Clinically used cilnidipine and progesterone, which have neuroprotective effects in animal ischemia models, were identified as inhibitors of hemichannel opening. These findings suggest that altered transport dynamics at the human BBB in the absence of extracellular Ca(2+) is at least partly attributable to opening of Px1 and Cx43 hemichannels. Therefore, we speculate that Px1 and Cx43 may be potential drug targets to ameliorate BBB transport dysregulation during acute ischemia.

Report this publication

Statistics

Seen <100 times