Inwardly Rectifying Potassium Channel Kir4.1 as a Novel Modulator of BDNF Expression in Astrocytes.
Inwardly Rectifying Potassium Channel Kir4.1 as a Novel Modulator of BDNF Expression in Astrocytes.
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DOI：
10.3390/ijms19113313
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发表时间：
2018-10-24
影响因子：
5.6
通讯作者：
Shimizu S
中科院分区：
文献类型：
--
作者：
Ohno Y;Kinboshi M;Shimizu S
脑源性神经营养因子(BDNF)是神经可塑性和发育所必需的关键分子，参与多种中枢神经系统(CNS)疾病的病理生理过程。目前研究表明，BDNF不仅在神经元中合成，而且在星形胶质细胞中合成，星形胶质细胞通过形成三部分突触来积极调节神经元的活动。星形胶质细胞特异表达的内向整流钾通道亚基Kir4.1构建了Kir4.1和Kir4.1/5.1通道，并介导星形胶质细胞的空间钾缓冲作用。最近的证据表明，Kir4.1通道在抗抑郁药物的作用和调节星形胶质细胞中BDNF的表达方面发挥了重要作用。虽然确切的机制尚不清楚，但抑制(下调或阻断)星形胶质细胞Kir4.1通道可能会减弱K+缓冲，通过升高细胞外K+和谷氨酸来增加神经元的兴奋性，并促进BDNF的表达。相反，Kir4.1通道的激活(上调或开放)通过降低细胞外K+和谷氨酸来降低神经元的兴奋性，并减弱BDNF的表达。特别是，前者的病理生理改变似乎在癫痫的发生和痛敏中起重要作用，而后者则在抑郁症的发病机制中起重要作用。本文综述了Kir4.1通道的功能，重点介绍了它们对星形胶质细胞空间K+缓冲和BDNF表达的调节，并讨论了星形胶质细胞Kir4.1-BDNF系统在调控中枢神经系统紊乱中的作用。
Brain-derived neurotrophic factor (BDNF) is a key molecule essential for neural plasticity and development, and is implicated in the pathophysiology of various central nervous system (CNS) disorders. It is now documented that BDNF is synthesized not only in neurons, but also in astrocytes which actively regulate neuronal activities by forming tripartite synapses. Inwardly rectifying potassium (Kir) channel subunit Kir4.1, which is specifically expressed in astrocytes, constructs Kir4.1 and Kir4.1/5.1 channels, and mediates the spatial potassium (K+) buffering action of astrocytes. Recent evidence illustrates that Kir4.1 channels play important roles in bringing about the actions of antidepressant drugs and modulating BDNF expression in astrocytes. Although the precise mechanisms remain to be clarified, it seems likely that inhibition (down-regulation or blockade) of astrocytic Kir4.1 channels attenuates K+ buffering, increases neuronal excitability by elevating extracellular K+ and glutamate, and facilitates BDNF expression. Conversely, activation (up-regulation or opening) of Kir4.1 channels reduces neuronal excitability by lowering extracellular K+ and glutamate, and attenuates BDNF expression. Particularly, the former pathophysiological alterations seem to be important in epileptogenesis and pain sensitization, and the latter in the pathogenesis of depressive disorders. In this article, we review the functions of Kir4.1 channels, with a focus on their regulation of spatial K+ buffering and BDNF expression in astrocytes, and discuss the role of the astrocytic Kir4.1-BDNF system in modulating CNS disorders.
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