Activation of Pannexin-1 Hemichannels Augments Aberrant Bursting in the Hippocampus
Activation of Pannexin-1 Hemichannels Augments Aberrant Bursting in the Hippocampus
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DOI：
10.1126/science.1165209
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发表时间：
2008-12-05
期刊：
影响因子：
56.9
通讯作者：
MacVicar, Brian A.
中科院分区：
文献类型：
--
作者：
Thompson, Roger J.;Jackson, Michael F.;MacVicar, Brian A.
Pannexin- 1 （Px1）在锥体神经元的突触后位点表达，表明这些半通道参与突触功能相关的树突信号。我们发现，在锥体神经元中，N-甲基- D-天冬氨酸受体（NMDAR）的激活诱导了二次延长电流和染料通量，这些电流和染料通量被一种针对Px1半通道的特异性抑制肽阻断；通过RNA干扰敲低Px1可阻断培养神经元中的电流。通过去除外源性镁离子（Mg2+）增强脑切片内源性NMDAR的激活可触发癫痫样活动，应用Px1半通道阻断肽可降低峰幅和延长爆发间隔。我们得出结论，Px1半通道开放是由NMDAR刺激触发的，并可能导致癫痫样发作活动。
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.