Low extracellular Ca2+ conditions induce an increase in brain endothelial permeability that involves intercellular Ca2+ waves

被引:41
|
作者
De Bock, Marijke [1 ]
Culot, Maxime [2 ]
Wang, Nan [1 ]
da Costa, Anaelle [2 ]
Decrock, Elke [1 ]
Bol, Melissa [1 ]
Bultynck, Geert [3 ]
Cecchelli, Romeo [2 ]
Leybaert, Luc [1 ]
机构
[1] Univ Ghent, Physiol Grp, Dept Basic Med Sci, B-9000 Ghent, Belgium
[2] Univ Lille Nord France, Fac Jean Perrin, Lab Physiopathol Barriere Hematoencephal, F-62307 Lens, France
[3] KULeuven, Lab Mol & Cellular Signaling, B-3000 Louvain, Belgium
关键词
Blood-brain barrier; Calcium wave; Calcium oscillation; Gap junction; Tight junction; PROTEIN-KINASE-C; ATP RELEASE; TIGHT JUNCTIONS; CALCIUM WAVE; MECHANICAL STIMULATION; CONNEXIN HEMICHANNELS; GAP-JUNCTIONS; K1; INVASION; BARRIER; COMMUNICATION;
D O I
10.1016/j.brainres.2012.06.046
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The intracellular calcium concentration ([Ca2+](i)) is an important factor determining the permeability of endothelial barriers including the blood-brain barrier (BBB). However, nothing is known concerning the effect of spatially propagated intercellular Ca2+ waves (ICWs). The propagation of ICWs relies in large part on channels formed by connexins that are present in endothelia. We hypothesized that ICWs may result in a strong disturbance of endothelial function, because the [Ca2+](i) changes are coordinated and involve multiple cells. Thus, we aimed to investigate the effect of ICWs on endothelial permeability. ICW activity was triggered in immortalized and primary brain endothelial cells by lowering the extracellular Ca2+ concentration. Low extracellular Ca2+ increased the endothelial permeability and this was significantly suppressed by buffering [Ca2+](i) with BAPTA-AM, indicating a central role of [Ca2+](i) changes. The endothelial permeability increase was furthermore inhibited by the connexin channel blocking peptide Gap27, which also blocked the ICWs, and by inhibiting protein kinase C (PKC), Ca2+/calmodulin-dependent kinase II (CaMKII) and actomyosin contraction. We compared these observations with the [Ca2+](i) changes and permeability alterations provoked by the inflammatory agent bradykinin (BK), which triggers oscillatory [Ca2+](i) changes without wave activity. BK-associated [Ca2+](i) changes and the endothelial permeability increase were significantly smaller than those associated with ICWs, and the permeability increase was not influenced by inhibition of PKC, CaMKII or actomyosin contraction. We conclude that ICWs significantly increase endothelial permeability and therefore, the connexins that underlie wave propagation form an interesting target to limit BBB alterations. This article is part of a Special Issue entitled Electrical Synapses. (C) 2012 Elsevier BM. All rights reserved.
引用
收藏
页码:78 / 87
页数:10
相关论文
共 50 条
  • [41] Three-dimensional model of intracellular and intercellular Ca2+ waves propagation in endothelial cells
    Sera, Toshihiro
    Komine, Shingo
    Arai, Masataka
    Sunaga, Yasuhiro
    Yokota, Hideo
    Kudo, Susumu
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2018, 505 (03) : 781 - 786
  • [42] The effects of mitochondrial Ca2+ transport on intracellular Ca2+ waves in cardiomyocytes
    Zhenghang Zhao
    Dandan Xiao
    Nadezhda Fefelova
    Lai-Hua Xie
    Journal of Translational Medicine, 10 (Suppl 2)
  • [43] [Ca2+](i) oscillations and [Ca2+](i) waves in rat megakaryocytes
    Tertyshnikova, S
    Fein, A
    CELL CALCIUM, 1997, 21 (05) : 331 - 344
  • [44] DEPLETION AND REFILLING OF INTRACELLULAR CA2+ STORES INDUCE OSCILLATIONS OF CA2+ CURRENT
    VACA, L
    KUNZE, DL
    AMERICAN JOURNAL OF PHYSIOLOGY, 1993, 264 (04): : H1319 - H1322
  • [45] Synchronized Ca2+ signaling by intercellular propagation of Ca2+ action potentials in NRK fibroblasts
    De Roos, ADG
    Willems, PHGM
    van Zoelen, EJJ
    Theuvenet, APR
    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1997, 273 (06): : C1900 - C1907
  • [46] CYTOSOLIC CA2+ OVERLOAD AND MACROMOLECULE PERMEABILITY OF ENDOTHELIAL MONOLAYERS
    PIPER, HM
    NOLL, T
    MUHS, A
    BESSELMANN, M
    KUHNE, W
    WATANABE, H
    HERZ, 1992, 17 (05) : 277 - 283
  • [47] Ca2+ homeostasis in brain microvascular endothelial cells
    Stoica, Roberta
    Rusu, Calin Mircea
    Staicu, Cristina Elena
    Burlacu, Andreea Elena
    Radu, Mihai
    Radu, Beatrice Mihaela
    INTER-ORGANELLAR CA2+ SIGNALING IN HEALTH AND DISEASE - PT A, 2021, 362 : 55 - 110
  • [48] Molecular Characterization of the Ca2+ Release Activated Ca2+ Current in Native Brain Capillary Endothelial Cells
    Sanchez, Alfredo
    Lavanderos, Boris
    Trebak, Mohamed
    Earley, Scott
    PHYSIOLOGY, 2024, 39
  • [49] Mutations associated with hypoparathyroidism increase Ca2+ receptor sensitivity to extracellular Ca2+.
    Krapcho, KJ
    DeLuca, F
    Pedersen, AT
    Gore, P
    Cutler, GB
    Nemeth, EF
    Baron, J
    JOURNAL OF BONE AND MINERAL RESEARCH, 1996, 11 : 107 - 107
  • [50] Paradoxical effect of ethanol on Ca2+ currents versus intracellular Ca2+ in endothelial cells of brain capillaries
    Barrios, Y
    Alvarez, R
    Altura, B
    Delpiano, MA
    PLACENTA, 2006, 27 (01) : A46 - A46