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Science:一种神经细胞离子通道激活导致癫痫病

来源:EurekAlert! 2008-12-05 10:28

专题:Science报道

据12月4日的《科学》杂志报道说,研究人员已经找到了一种存在于神经细胞中的特别的离子通道,当这种离子通道过度活跃的时候会在脑子的海马回中引起一种“脉冲”活动,这与在癫痫发作的时候所经历的情况类似。这一发现可能会对癫痫和中风的治疗提供一种新型的治疗标靶。

Roger Thompson及其同僚培养了海马回中的神经元,接着用全细胞膜片钳技术来激活这些离子通道并记录它们的活动。这种方法阻断了细胞中的依赖于电压激活的离子通道,使得研究人员可以观察并记录通过细胞的继发性的电流。他们发现,这种继发性电流中的一种(由蛋白Pannexin-1所形成的一种半通道)在当某种特别的叫做NMDAR的受体过度激活的时候,容易发生癫痫样的活动。研究人员说,人们需要对Pannexin-1半通道进行认真的研究以发现其在癫痫中所起的特别的作用,它可能最终会引领人们找到有效治疗某些神经系统疾病的途径。(生物谷Bioon.com)

生物谷推荐原始出处:

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

Roger J. Thompson,1* Michael F. Jackson,2 Michelle E. Olah,2 Ravi L. Rungta,1 Dustin J. Hines,1 Michael A. Beazely,2 John F. MacDonald,2 Brian A. MacVicar1

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.

1 Department of Psychiatry and Brain Research Centre, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada.
2 Robarts Research Institute, University of Western Ontario, London, ON N6A 5K8, Canada.

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