Ischemia opens neuronal gap junction hemichannels

被引：440

作者：

Thompson, RJ

Zhou, N

MacVicar, BA ^{[1
]}

机构：

[1] Univ British Columbia, Dept Psychiat, Vancouver, BC V6T 2B5, Canada

[2] Univ British Columbia, Brain Res Ctr, Vancouver, BC V6T 2B5, Canada

来源：

SCIENCE | 2006年 / 312卷 / 5775期

关键词：

D O I：

10.1126/science.1126241

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Neuronal excitotoxicity during stroke is caused by activation of unidentified large-conductance channels, leading to swelling and calcium dysregulation. We show that ischemic-like conditions [O-2/glucose deprivation (OGD)] open hemichannels, or half gap junctions, in neurons. Hemichannel opening was indicated by a large linear current and flux across the membrane of small fluorescent molecules. Single-channel openings of hemichannels ( 530 picosiemens) were observed in OGD. Both the current and dye flux were blocked by inhibitors of hemichannels. Therefore, hemichannel opening contributes to the profound ionic dysregulation during stroke and may be a ubiquitous component of ischemic neuronal death.

引用

收藏

页码：924 / 927

页数：4

相关论文

共 23 条

[1] A key role for TRPM7 channels in anoxic neuronal death [J].

Aarts, M ;

Iihara, K ;

Wei, WL ;

Xiong, ZG ;

Arundine, M ;

Cerwinski, W ;

MacDonald, JF ;

Tymianski, M .

CELL, 2003, 115 (07) :863-877

[2] Blocking the anoxic depolarization protects without functional compromise following simulated stroke in cortical brain slices [J].

Anderson, TR ;

Jarvis, CR ;

Biedermann, AJ ;

Molnar, C ;

Andrew, RD .

JOURNAL OF NEUROPHYSIOLOGY, 2005, 93 (02) :963-979

[3] Pannexin membrane channels are mechanosensitive conduits for ATP [J].

Bao, L ;

Locovei, S ;

Dahl, G .

FEBS LETTERS, 2004, 572 (1-3) :65-68

[4] ELEVATION OF THE EXTRACELLULAR CONCENTRATIONS OF GLUTAMATE AND ASPARTATE IN RAT HIPPOCAMPUS DURING TRANSIENT CEREBRAL-ISCHEMIA MONITORED BY INTRACEREBRAL MICRODIALYSIS [J].

BENVENISTE, H ;

DREJER, J ;

SCHOUSBOE, A ;

DIEMER, NH .

JOURNAL OF NEUROCHEMISTRY, 1984, 43 (05) :1369-1374

[5] Pharmacological properties of homomeric and heteromeric pannexin hemichannels expressed in Xenopus oocytes [J].

Bruzzone, R ;

Barbe, MT ;

Jakob, NJ ;

Monyer, H .

JOURNAL OF NEUROCHEMISTRY, 2005, 92 (05) :1033-1043

[6] Pannexins, a family of gap junction proteins expressed in brain [J].

Bruzzone, R ;

Hormuzdi, SG ;

Barbe, MT ;

Herb, A ;

Monyer, H .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (23) :13644-13649

[7] Metabolic inhibition induces opening of unapposed connexin 43 gap junction hemichannels and reduces gap junctional communication in cortical astrocytes in culture [J].

Contreras, JE ;

Sánchez, HA ;

Eugenin, EA ;

Speidel, D ;

Theis, M ;

Willecke, K ;

Bukauskas, FF ;

Bennett, MVL ;

Sáez, JC .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (01) :495-500

[8] Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP [J].

Feng, GP ;

Mellor, RH ;

Bernstein, M ;

Keller-Peck, C ;

Nguyen, QT ;

Wallace, M ;

Nerbonne, JM ;

Lichtman, JW ;

Sanes, JR .

NEURON, 2000, 28 (01) :41-51

[9] Anoxia-induced depolarization in CA1 hippocampal neurons: role of Na+-dependent mechanisms [J].

Fung, ML ;

Haddad, GG .

BRAIN RESEARCH, 1997, 762 (1-2) :97-102

[10] Coupling between NMDA receptor and acid-sensing ion channel contributes to ischemic neuronal death [J].

Gao, J ;

Duan, B ;

Wang, DG ;

Deng, XH ;

Zhang, GY ;

Xu, L ;

Xu, TL .

NEURON, 2005, 48 (04) :635-646