Emerging Roles of Astrocyte Kir4.1 Channels in the Pathogenesis and Treatment of Brain Diseases.
Emerging Roles of Astrocyte Kir4.1 Channels in the Pathogenesis and Treatment of Brain Diseases.
复制标题
DOI：
10.3390/ijms221910236
复制
发表时间：
2021-09-23
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;Kunisawa N;Shimizu S
星形胶质细胞中的抑制整流Kir4.1通道介导空间钾（K+）缓冲，这是三联突触中过量细胞外K+的清除机制。除了K+稳态外，星形胶质细胞Kir4.1通道还通过与谷氨酸转运体偶联在调节细胞外谷氨酸水平中发挥重要作用。此外，Kir4.1通道作为脑源性神经营养因子（BDNF）在星形胶质细胞中的表达的新的调制器。具体地说，抑制星形胶质细胞Kir4.1通道可提高突触处的细胞外K+和谷氨酸水平，并促进星形胶质细胞中BDNF的表达。这些变化提高了神经兴奋性，这可能有助于突触可塑性和连接性。本文综述了星形胶质细胞Kir4.1通道的功能和药理学特性，并强调了这些通道在脑疾病治疗中的重要性。虽然需要在动物模型和人类患者中进行进一步验证，但星形胶质细胞Kir4.1通道可能成为治疗抑郁症和癫痫的新靶点。
Inwardly rectifying Kir4.1 channels in astrocytes mediate spatial potassium (K+) buffering, a clearance mechanism for excessive extracellular K+, in tripartite synapses. In addition to K+ homeostasis, astrocytic Kir4.1 channels also play an essential role in regulating extracellular glutamate levels via coupling with glutamate transporters. Moreover, Kir4.1 channels act as novel modulators of the expression of brain-derived neurotrophic factor (BDNF) in astrocytes. Specifically, inhibition of astrocytic Kir4.1 channels elevates extracellular K+ and glutamate levels at synapses and facilitates BDNF expression in astrocytes. These changes elevate neural excitability, which may facilitate synaptic plasticity and connectivity. In this article, we summarize the functions and pharmacological features of Kir4.1 channels in astrocytes and highlight the importance of these channels in the treatment of brain diseases. Although further validation in animal models and human patients is required, astrocytic Kir4.1 channel could potentially serve as a novel therapeutic target for the treatment of depressive disorders and epilepsy.
登录
查看更多内容
影响因子：
5.3
作者：
Djukic, Biljana;Casper, Kristen B.;McCarthy, Ken D.
通讯作者：
McCarthy, Ken D.
影响因子：
3.6
作者：
Furutani, Kazuharu;Ohno, Yukihiro;Kurachi, Yoshihisa
通讯作者：
Kurachi, Yoshihisa
影响因子：
81.5
作者：
Colloca, Luana;Ludman, Taylor;Raja, Srinivasa N.
通讯作者：
Raja, Srinivasa N.
外侧缰核中的星形胶质细胞 Kir4.1 驱动抑郁症中的神经元爆发
影响因子：
64.8
作者：
Cui, Yihui;Yang, Yan;Hu, Hailan
通讯作者：
Hu, Hailan
影响因子：
2.2
作者：
Banerjee, Poonam Nina;Filippi, David;Hauser, W. Allen
通讯作者：
Hauser, W. Allen