Genetic Deletion of TREK-1 or TWIK-1/TREK-1 Potassium Channels does not Alter the Basic Electrophysiological Properties of Mature Hippocampal Astrocytes In Situ.
Genetic Deletion of TREK-1 or TWIK-1/TREK-1 Potassium Channels does not Alter the Basic Electrophysiological Properties of Mature Hippocampal Astrocytes In Situ.
复制标题
TREK-1 或 TWIK-1/TREK-1 钾通道的基因删除不会原位改变成熟海马星形胶质细胞的基本电生理特性
DOI：
10.3389/fncel.2016.00013
复制
发表时间：
2016
影响因子：
5.3
通讯作者：
Zhou M
中科院分区：
文献类型：
--
作者：
Du Y;Kiyoshi CM;Wang Q;Wang W;Ma B;Alford CC;Zhong S;Wan Q;Chen H;Lloyd EE;Bryan RM Jr;Zhou M
我们最近发现，膜电导（被动电导）的线性电流-电压（I-V）关系反映了成熟星形胶质细胞中K+通道的内在特性。虽然已知被动电导支持星形胶质细胞的基本稳态功能所必需的高度负性和稳定的膜电位（VM），但所涉及的K+通道的完整库仍然难以捉摸。TREK-1双孔结构域K+通道（K2 P）在星形胶质细胞中高度表达，并且TREK-1与TWIK-1（另一种高度表达的星形胶质细胞K2 P）的共价缔合已被报道为异源二聚体TWIK-1/TREK-1通道运输至膜并促成星形胶质细胞被动传导的潜在机制。为了解释TREK-1的个体贡献并解决被动传导的出现是否取决于星形胶质细胞中TWIK-1/TREK-1的共表达，在本研究中使用TREK-1单基因敲除小鼠和TWIK-1/TREK-1双基因敲除小鼠。在这些基因敲除小鼠中，编码其他星形胶质细胞K+通道（如Kir4.1、Kir5.1和TREK-2）的mRNA的相对数量没有改变。海马星形胶质细胞原位全细胞记录显示，在两种基因敲除小鼠中，星形胶质细胞被动电导、VM或膜输入电阻（Rin）均未检测到变化。此外，TREK-1蛋白主要位于海马的细胞内区室。总而言之，单独或与TWIK-1一起基因缺失TREK-1不会对海马星形胶质细胞的基本电生理特性产生明显改变。因此，未来的研究重点是其他K+通道可能揭示这个长期存在的重要问题，在星形胶质细胞生理学。
We have recently shown that a linear current-to-voltage (I-V) relationship of membrane conductance (passive conductance) reflects the intrinsic property of K+ channels in mature astrocytes. While passive conductance is known to underpin a highly negative and stable membrane potential (VM) essential for the basic homeostatic function of astrocytes, a complete repertoire of the involved K+ channels remains elusive. TREK-1 two-pore domain K+ channel (K2P) is highly expressed in astrocytes, and covalent association of TREK-1 with TWIK-1, another highly expressed astrocytic K2P, has been reported as a mechanism underlying the trafficking of heterodimer TWIK-1/TREK-1 channel to the membrane and contributing to astrocyte passive conductance. To decipher the individual contribution of TREK-1 and address whether the appearance of passive conductance is conditional to the co-expression of TWIK-1/TREK-1 in astrocytes, TREK-1 single and TWIK-1/TREK-1 double gene knockout mice were used in the present study. The relative quantity of mRNA encoding other astrocyte K+ channels, such as Kir4.1, Kir5.1, and TREK-2, was not altered in these gene knockout mice. Whole-cell recording from hippocampal astrocytes in situ revealed no detectable changes in astrocyte passive conductance, VM, or membrane input resistance (Rin) in either kind of gene knockout mouse. Additionally, TREK-1 proteins were mainly located in the intracellular compartments of the hippocampus. Altogether, genetic deletion of TREK-1 alone or together with TWIK-1 produced no obvious alteration in the basic electrophysiological properties of hippocampal astrocytes. Thus, future research focusing on other K+ channels may shed light on this long-standing and important question in astrocyte physiology.