Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel
Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel
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DOI：
10.1002/j.1460-2075.1996.tb01077.x
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发表时间：
1996-12-16
期刊：
影响因子：
11.4
通讯作者：
Lazdunski, M
中科院分区：
文献类型：
--
作者：
Fink, M;Duprat, F;Lazdunski, M
人TWIK-1是新近克隆的一种新型内向整流钾通道。本文报道了TREK-1的结构和功能特性，TREK-1是哺乳动物TWIK-1相关的K+通道，尽管TWIK-1和TREK-1之间的氨基酸同源性较低（类似于28%），两种通道蛋白共享由两个孔形成结构域和四个跨膜区段（TMS）组成的相同的总体结构排列。这种结构相似性不会产生功能类似性，由TWIK-1产生的K+电流是向内整流的，而由TREK-1产生的K+电流是向外整流的，这些通道具有14 pS的电导，TREK-1电流对阻断TWIK-1活性的药理学试剂（如奎宁和奎尼丁）不敏感，在蛋白激酶A和C活化后观察到TREK-1活性的广泛抑制。TREK-1电流对细胞外K+和Na+敏感。TREK-1 mRNA在大多数组织中表达，并且在肺和脑中特别丰富，已经通过原位杂交研究了其在脑组织中的定位。TREK-1在嗅球、海马和小脑中高表达。这些结果首次证明哺乳动物神经系统中存在一个具有4个TMS和2个孔结构域的K+通道家族，并表明该结构家族中不同成员可能具有完全不同的功能特性。
Human TWIK-1, which has been cloned recently, is a new structural type of weak inward rectifier K+ channel. Here we report the structural and functional properties of TREK-1, a mammalian TWIK-1-related K+ channel, Despite a low amino acid identity between TWIK-1 and TREK-1 (similar to 28%), both channel proteins share the same overall structural arrangement consisting of two pore-forming domains and four transmembrane segments (TMS), This structural similarity does not give rise to a functional analogy, K+ currents generated by TWIK-1 are inwardly rectifying while K+ currents generated by TREK-1 are outwardly rectifying, These channels have a conductance of 14 pS, TREK-1 currents are insensitive to pharmacological agents that block TWIK-1 activity such as quinine and quinidine, Extensive inhibitions of TREK-1 activity are observed after activation of protein kinases A and C. TREK-1 currents are sensitive to extracellular K+ and Na+. TREK-1 mRNA is expressed in most tissues and is particularly abundant in the lung and in the brain, Its localization in this latter tissue has been studied by in situ hybridization. TREK-1 expression is high in the olfactory bulb, hippocampus and cerebellum, These results provide the first evidence for the existence of a K+ channel family with four TMS and two pore domains in the nervous system of mammals, They also show that different members in this structural family can have totally different functional properties.