Highly conductive carbon nanotube matrix accelerates developmental chloride extrusion in central nervous system neurons by increased expression of chloride transporter KCC2.
Highly conductive carbon nanotube matrix accelerates developmental chloride extrusion in central nervous system neurons by increased expression of chloride transporter KCC2.
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DOI：
10.1002/smll.201201994
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发表时间：
2013-04-08
期刊：
影响因子：
13.3
通讯作者：
Liu, Jie
中科院分区：
文献类型：
--
作者：
Liedtke, Wolfgang;Yeo, Michele;Zhang, Hongbo;Wang, Yiding;Gignac, Michelle;Miller, Sara;Berglund, Ken;Liu, Jie
碳纳米管（CNT）卓越的机械和电气性能吸引了神经科学家和神经组织工程师，旨在开发与神经组织接口的新型设备。在中枢神经系统（CNS）中，围产期氯转移代表了一种动态变化，其形成了γ-氨基丁酸（GABA）作为抑制性神经递质的生理作用的基础，这是一种与CNS正常功能基本相关的过程。低的神经元内氯化物浓度由氯化物挤压转运蛋白氯化钾协同转运蛋白2（KCC 2）维持。KCC 2在发育过程中表达的增加是氯离子转移的基础。在神经损伤中，抑制的KCC 2表达通过破坏抑制性神经传递起共同作用。因此，Kcc 2上调的机制是相关的，因为它们的医学相关性，但它们仍然难以捉摸。在这里，我们表明，原发性中枢神经系统神经元来自大脑皮层，培养高导电少壁碳纳米管（fwCNT）有一个显着加速氯离子移位增加KCC 2的表达所造成的。KCC 2上调依赖于神经元电压门控钙通道（VGCC），此外还依赖于钙/钙调蛋白依赖性激酶II，后者与VGCC介导的钙内流有关。我们还证明了加速Kcc 2转录从基因工程报告小鼠，其中Kcc 2启动子驱动荧光素酶，当这些小鼠的大脑皮层暴露于fwCNT涂层的设备制备的脑切片。基于这些发现，我们现在可以解决fwCNT是否可以增强神经工程装置，以有利于与神经元细胞内氯离子浓度升高相关的神经损伤状况，如疼痛、癫痫、创伤性神经损伤和缺血。总之，我们的新见解说明了fwCNTs如何促进单个神经元中的低神经元氯化物，从而抑制神经回路中的传递。
Exceptional mechanical and electrical properties of carbon nanotubes (CNT) have attracted neuroscientists and neural tissue engineers aiming to develop novel devices that interface with nervous tissues. In the central nervous system (CNS), the perinatal chloride shift represents a dynamic change that forms the basis for physiological actions of γ-aminobutyric acid (GABA) as inhibitory neurotransmitter, a process of fundamental relevance for normal functioning of the CNS. Low intra-neuronal chloride concentrations are maintained by chloride-extruding transporter, potassium chloride cotransporter 2 (KCC2). KCC2's increasing developmental expression underlies the chloride shift. In neural injury, repressed KCC2 expression plays a co-contributory role by corrupting inhibitory neurotransmission. Mechanisms of Kcc2 up-regulation are thus pertinent because of their medical relevance, yet they remain elusive. Here we show that primary CNS neurons originating from the cerebral cortex, cultured on highly-conductive few-walled-CNT (fwCNT) have a strikingly accelerated chloride shift caused by increased KCC2 expression. KCC2 upregulation is dependent on neuronal voltage-gated calcium channels (VGCC), furthermore on calcium/calmodulin-dependent kinase II, which is linked to VGCC-mediated calcium-influx. We also demonstrate accelerated Kcc2 transcription in brain-slices prepared from genetically-engineered reporter mice, in which Kcc2 promoter drives luciferase, when the cerebral cortex of these mice is exposed to fwCNT-coated devices. Based on these findings, we can now address whether fwCNT can enhance neural engineering devices for the benefit of neural injury conditions associated with elevated neuronal intracellular chloride concentration such as pain, epilepsy, traumatic neural injury and ischemia. Taken together, our novel insights illustrate how fwCNTs can promote low neuronal chloride in individual neurons and thus inhibitory transmission in neural circuits.
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