A mammalian transient type K+ channel, rat Kv1.4, has two potential domains that could produce rapid inactivation

A mammalian transient type K+ channel, rat Kv1.4, has two potential domains that could produce rapid inactivation
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DOI:
10.1074/jbc.272.31.19333
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发表时间:
1997-08-01
影响因子:
4.8
通讯作者:
Taira, N
Taira, N
中科院分区:
生物学2区
文献类型:
--
作者:
Kondoh, S;Ishii, K;Taira, N

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‘’球和链‘’模型已被证明适用于解释电压依赖的K+通道的快速失活,对于果蝇振荡器K+通道(SHB),氨基末端的前20个残基已被确定为结合到开放通道孔并阻止离子流动的失活球(Hoshi,T.,Zagotta,W.N.,and Aldrich,R.W.(1990)Science 250,533-538;Zagotta,W.N.,Hoshi,T.,and Aldrich,R.W.(1990)Science 250,568-571),我们通过在非洲爪哇卵母细胞的氨基末端构建各种突变体并表达它们来研究导致哺乳动物暂时性K+通道(大鼠Kv1.4)快速失活的结构元件,尽管已有报道最初的37个残基可能形成大鼠Kv1.4的失活球(Tseng-Crank,J.,姚,J.-A.,Berman M.F.,和Tseng,G.-N(1993)J.Physiol,102,1057-1083),我们发现不仅最初的37个残基,而且接下来的40-68残基也可以独立起失活门的作用,就像Shaker失活球一样,这两个潜在的失活结构域都有一个疏水的氨基末端和一个带净正电荷的亲水羧基末端,这是这些结构域作为失活门发挥作用所必需的。
The ''ball and chain'' model has been shown to be suitable for explaining the rapid inactivation of voltage-dependent K+ channels, For the Drosophila Shaker K+ channel (ShB), the first 20 residues of the amino terminus have been identified as the inactivation ball that binds to the open channel pore and blocks ion flow (Hoshi, T., Zagotta, W. N., and Aldrich, R. W. (1990) Science 250, 533-538; Zagotta, W. N., Hoshi, T., and Aldrich, R. W. (1990) Science 250, 568-571), We studied the structural elements responsible for rapid inactivation of a mammalian transient type K+ channel (rat Kv1.4) by constructing various mutants in the amino terminus and expressing them in Xenopus oocytes, Although it has been reported that the initial 37 residues might form the inactivation ball for rat Kv1.4 (Tseng-Crank, J., Yao, J.-A., Berman M. F., and Tseng, G.-N. (1993) J. Gen. Physiol, 102, 1057-1083), we found that not only the initial 37 residues, but also the following region, residues 40-68, could function independently as an inactivation gate, Like the Shaker inactivation ball, both potential inactivation domains have a hydrophobic amino-terminal region and a hydrophilic carboxyl-terminal region having net positive charge, which is essential for the domains to function as an inactivation gate.