Twenty years of fluorescence imaging of intracellular chloride.

Twenty years of fluorescence imaging of intracellular chloride.
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DOI:
10.3389/fncel.2014.00258
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发表时间:
2014
影响因子:
5.3
通讯作者:
Ratto GM
Ratto GM
中科院分区:
医学2区
文献类型:
--
作者:
Arosio D;Ratto GM

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氯离子稳态在控制成人大脑和发育过程中的神经元兴奋性中起着关键作用。细胞内氯离子浓度受膜传导的被动通量和进口和出口介导的主动转运之间的动态平衡调节。在皮质神经元中,氯离子通量通过打开嗜离子性GABAA受体与网络活动耦合,这在中间神经元的活动和氯离子通量之间提供了直接联系。这些分子机制在神经元表面的分布和调节并不均匀,这一事实可能导致细胞内氯离子浓度的区隔控制。GABAA受体的活性所提供的抑制驱动取决于相关电流的方向和强度,最终由氯离子的梯度决定,氯离子是流经GABAA通道的主要电荷载体。因此,细胞内氯离子的分布决定了局部的亲离子抑制强度,并影响了收敛激发和抑制之间的相互作用。氯化物调节的重要性也因其在包括癫痫和自闭症谱系障碍在内的几种脑病中的作用而得到强调。要充分理解gaba能在神经元上的生理意义,需要测量氯离子跨膜通量的时空动态。如今,有几种可用的工具来完成这项任务,合成和基因编码的指示器都已成功地用于氯化物成像。在这里,我们将回顾现有的传感器,分析其特性并概述理想的未来发展。
Chloride homeostasis has a pivotal role in controlling neuronal excitability in the adult brain and during development. The intracellular concentration of chloride is regulated by the dynamic equilibrium between passive fluxes through membrane conductances and the active transport mediated by importers and exporters. In cortical neurons, chloride fluxes are coupled to network activity by the opening of the ionotropic GABAA receptors that provides a direct link between the activity of interneurons and chloride fluxes. These molecular mechanisms are not evenly distributed and regulated over the neuron surface and this fact can lead to a compartmentalized control of the intracellular concentration of chloride. The inhibitory drive provided by the activity of the GABAA receptors depends on the direction and strength of the associated currents, which are ultimately dictated by the gradient of chloride, the main charge carrier flowing through the GABAA channel. Thus, the intracellular distribution of chloride determines the local strength of ionotropic inhibition and influences the interaction between converging excitation and inhibition. The importance of chloride regulation is also underlined by its involvement in several brain pathologies, including epilepsy and disorders of the autistic spectra. The full comprehension of the physiological meaning of GABAergic activity on neurons requires the measurement of the spatiotemporal dynamics of chloride fluxes across the membrane. Nowadays, there are several available tools for the task, and both synthetic and genetically encoded indicators have been successfully used for chloride imaging. Here, we will review the available sensors analyzing their properties and outlining desirable future developments.
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