TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a novel structure
TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a novel structure
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DOI：
10.1002/j.1460-2075.1996.tb00437.x
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发表时间：
1996-03-01
期刊：
影响因子：
11.4
通讯作者：
Barhanin, J
中科院分区：
文献类型：
--
作者：
Lesage, F;Guillemare, E;Barhanin, J
一种新的人类弱内向整流K+通道TWIK-1已被分离出来，该通道长336个氨基酸，具有四个跨膜结构域，与其他哺乳动物K+通道不同，它包含两个称为P结构域的成孔区域，编码结构同源物的基因存在于秀丽隐杆线虫的基因组中，爪蟾卵母细胞中表达的TWIK-1电流是 与时间无关，并呈现出近乎线性的 I-V 关系，在存在内部 Mg2+ 的情况下，去极化正向饱和到 0 mV。在没有内部 Mg2+ 的情况下，这种向内整流被取消。TWIK-1 的单位电导为 34 pS，动力学行为依赖于膜电位。在存在内部 Mg2+ 的情况下，平均开放时间在 -80 和 1.9 毫秒时为 0.3 和 1.9 毫秒。 +80 mV，通道活性通过蛋白激酶C的激活上调，通过内部酸化下调，两种调节都是间接的，TWIK-1通道活性被Ba2+（IC50=100μM）、奎宁（IC50=50μM）和奎尼丁（IC50=95μM）阻断。该通道特别令人感兴趣，因为它的 mRNA 广泛分布在人体组织中，并且在大脑和心脏中特别丰富。 TWIK-1 通道可能参与背景 K+ 膜电导的控制。
A new human weakly inward rectifying K+ channel, TWIK-1, has been isolated, This channel is 336 amino acids long and has four transmembrane domains, Unlike other mammalian K+ channels, it contains two pore-forming regions called P domains, Genes encoding structural homologues are present in the genome of Caenorhabditis elegans, TWIK-1 currents expressed in Xenopus oocytes are time-independent and present a nearly linear I-V relationship that saturated for depolarizations positive to 0 mV in the presence of internal Mg2+, This inward rectification is abolished in the absence of internal Mg2+, TWIK-1 has a unitary conductance of 34 pS and a kinetic behaviour that is dependent on the membrane potential, In the presence of internal Mg2+, the mean open times are 0.3 and 1.9 ms at -80 and +80 mV, respectively, The channel activity is up-regulated by activation of protein kinase C and down-regulated by internal acidification, Both types of regulation are indirect, TWIK-1 channel activity is blocked by Ba2+ (IC50 = 100 mu M), quinine (IC50 = 50 mu M) and quinidine (IC50 = 95 mu M). This channel is of particular interest because its mRNA is widely distributed in human tissues, and is particularly abundant in brain and heart. TWIK-1 channels are probably involved in the control of background K+ membrane conductances.