Rose C R, Chatton J-Y
Institute of Neurobiology, Faculty of Mathematics and Natural Sciences, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, D-40225 Düsseldorf, Germany.
Department of Fundamental Neurosciences, University of Lausanne, rue du Bugnon 9, CH-1005 Lausanne, Switzerland.
Neuroscience. 2016 May 26;323:121-34. doi: 10.1016/j.neuroscience.2015.03.002. Epub 2015 Mar 16.
At tripartite synapses, astrocytes undergo calcium signaling in response to release of neurotransmitters and this calcium signaling has been proposed to play a critical role in neuron-glia interaction. Recent work has now firmly established that, in addition, neuronal activity also evokes sodium transients in astrocytes, which can be local or global depending on the number of activated synapses and the duration of activity. Furthermore, astrocyte sodium signals can be transmitted to adjacent cells through gap junctions and following release of gliotransmitters. A main pathway for activity-related sodium influx into astrocytes is via high-affinity sodium-dependent glutamate transporters. Astrocyte sodium signals differ in many respects from the well-described glial calcium signals both in terms of their temporal as well as spatial distribution. There are no known buffering systems for sodium ions, nor is there store-mediated release of sodium. Sodium signals thus seem to represent rather direct and unbiased indicators of the site and strength of neuronal inputs. As such they have an immediate influence on the activity of sodium-dependent transporters which may even reverse in response to sodium signaling, as has been shown for GABA transporters for example. Furthermore, recovery from sodium transients through Na(+)/K(+)-ATPase requires a measurable amount of ATP, resulting in an activation of glial metabolism. In this review, we present basic principles of sodium regulation and the current state of knowledge concerning the occurrence and properties of activity-related sodium transients in astrocytes. We then discuss different aspects of the relationship between sodium changes in astrocytes and neuro-metabolic coupling, putting forward the idea that indeed sodium might serve as a new type of intracellular ion signal playing an important role in neuron-glia interaction and neuro-metabolic coupling in the healthy and diseased brain.
在三方突触中，星形胶质细胞会响应神经递质的释放而产生钙信号，并且有人提出这种钙信号在神经元与神经胶质细胞的相互作用中起关键作用。最近的研究现已确凿证实，此外，神经元活动还会引发星形胶质细胞中的钠瞬变，根据激活突触的数量和活动持续时间，这种钠瞬变可以是局部的或全局性的。此外，星形胶质细胞的钠信号可以通过缝隙连接传递给相邻细胞，并在神经胶质递质释放后传递。与活动相关的钠流入星形胶质细胞的主要途径是通过高亲和力的钠依赖性谷氨酸转运体。星形胶质细胞的钠信号在时间和空间分布方面与已充分描述的胶质钙信号在许多方面都有所不同。目前还没有已知的钠离子缓冲系统，也不存在储存介导的钠释放。因此，钠信号似乎代表了神经元输入部位和强度的相当直接且无偏差的指标。正因如此，它们会对钠依赖性转运体的活性产生直接影响，例如，GABA转运体已被证明会因钠信号而发生逆转。此外，通过Na(+)/K(+)-ATP酶从钠瞬变中恢复需要一定量的ATP，从而导致神经胶质代谢的激活。在这篇综述中，我们阐述了钠调节的基本原理以及关于星形胶质细胞中与活动相关的钠瞬变的发生和特性的当前知识状态。然后，我们讨论了星形胶质细胞中钠变化与神经代谢耦合之间关系的不同方面，提出钠确实可能作为一种新型的细胞内离子信号，在健康和患病大脑的神经元与神经胶质细胞相互作用以及神经代谢耦合中发挥重要作用的观点。
