Activation of Pannexin-1 Hemichannels Augments Aberrant Bursting in the Hippocampus

被引：295

作者：

Thompson, Roger J. ^{[1
,2
]}

Jackson, Michael F. ^{[3
]}

Olah, Michelle E. ^{[3
]}

Rungta, Ravi L. ^{[1
,2
]}

Hines, Dustin J. ^{[1
,2
]}

Beazely, Michael A. ^{[3
]}

MacDonald, John F. ^{[3
]}

MacVicar, Brian A. ^{[1
,2
]}

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

[3] Univ Western Ontario, Robarts Res Inst, London, ON N6A 5K8, Canada

来源：

SCIENCE | 2008年 / 322卷 / 5907期

基金：

加拿大健康研究院;

关键词：

D O I：

10.1126/science.1165209

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：

Pannexin- 1 ( Px1) is expressed at postsynaptic sites in pyramidal neurons, suggesting that these hemichannels contribute to dendritic signals associated with synaptic function. We found that, in pyramidal neurons, N- methyl- D- aspartate receptor ( NMDAR) activation induced a secondary prolonged current and dye flux that were blocked with a specific inhibitory peptide against Px1 hemichannels; knockdown of Px1 by RNA interference blocked the current in cultured neurons. Enhancing endogenous NMDAR activation in brain slices by removing external magnesium ions (Mg2+) triggered epileptiform activity, which had decreased spike amplitude and prolonged interburst interval during application of the Px1 hemichannel blocking peptide. We conclude that Px1 hemichannel opening is triggered by NMDAR stimulation and can contribute to epileptiform seizure activity.

引用

页码：1555 / 1559

页数：5

共 18 条

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

Bao, L ;

Locovei, S ;

Dahl, G .

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

[2] Pyramid power: Principal cells of the hippocampus unite! [J].

Bennett, Michael V. L. ;

Pereda, Alberto .

BRAIN CELL BIOLOGY, 2006, 35 (01) :5-11

[3] 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

[4]

Chen QX, 1997, J NEUROSCI, V17, P4032

[5] Cumulative effects of glutamate microstimulation on Ca2+ responses of CA1 hippocampal pyramidal neurons in slice [J].

Connor, JA ;

Cormier, RJ .

JOURNAL OF NEUROPHYSIOLOGY, 2000, 83 (01) :90-98

[6] LATE LOW MAGNESIUM-INDUCED EPILEPTIFORM ACTIVITY IN RAT ENTORHINAL CORTEX SLICES BECOMES INSENSITIVE TO THE ANTICONVULSANT VALPROIC ACID [J].

DREIER, JP ;

HEINEMANN, U .

NEUROSCIENCE LETTERS, 1990, 119 (01) :68-70

[7] Pannexin1 is expressed by neurons and glia but does not form functional gap junctions [J].

Huang, Yan ;

Grinspan, Judith B. ;

Abrams, Charles K. ;

Scherer, Steven S. .

GLIA, 2007, 55 (01) :46-56

[8] Localized loss of Ca2+ Homeostasis in neuronal dendrites is a downstream consequence of metabolic compromise during extended NMDA exposures [J].

Jagt, Thomas A. Vander ;

Connor, John A. ;

Shuttleworth, C. William .

JOURNAL OF NEUROSCIENCE, 2008, 28 (19) :5029-5039

[9] Pannexin 1 in erythrocytes: Function without a gap [J].

Locovei, Silviu ;

Bao, Li ;

Dahl, Gerhard .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (20) :7655-7659

[10] Two-photon Imaging of stroke onset in vivo reveals that NMDA-receptor independent ischemic depolarization is the major cause of rapid reversible damage to dendrites and spines [J].

Murphy, Timothy H. ;

Li, Ping ;

Betts, Kellen ;

Liu, Richard .

JOURNAL OF NEUROSCIENCE, 2008, 28 (07) :1756-1772

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