Heteromultimeric interactions among K+ channel subunits from Shaker and eag families in Xenopus oocytes

Heteromultimeric interactions among K+ channel subunits from Shaker and eag families in Xenopus oocytes
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DOI:
10.1016/s0896-6273(00)80185-3
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发表时间:
1996-09-01
期刊:
影响因子:
16.2
通讯作者:
Wu, CF
Wu, CF
中科院分区:
医学1区
文献类型:
--
作者:
Chen, ML;Hoshi, T;Wu, CF

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不同家族的K+通道亚基的异多聚相互作用被认为有助于离子电流的功能多样性,正如先前的遗传证据所表明的那样。我们在此直接展示了非洲爪蟾卵母细胞中来自不同eag和Shaker家族的亚基在功能上相互作用,最有可能是异质多聚通道。与eag共表达加速了瞬态激振器电流失活并减缓了从失活中恢复的速度。位点定向诱变表明,卵磷脂羧基端对这种相互作用至关重要,优先对n型失活产生影响。现在已经确定了许多eag和Shaker家族的成员,它们的人类同源物与心脏和神经系统疾病有关。通道亚基相互作用的研究可能对理解疾病模式和大脑的复杂功能具有重要意义。
Heteromultimeric interactions of K+ channel subunits across different families have been thought to contribute to the functional diversity of ionic currents, as suggested by previous genetic evidence. We present here direct demonstration in Xenopus oocytes that subunits from distinct eag and Shaker families functionally interact, most likely as heteromultimeric channels. Coexpression with eag accelerates the inactivation and slows the recovery from inactivation of the transient Shaker current. Site-directed mutagenesis indicates that the eag carboxyl terminus is crucial for this interaction, exerting effects preferentially on N-type inactivation. Many members of the eag and Shaker families have now been identified and their human homologs implicated in cardiac and neurological disorders. Studies on channel subunit interactions may prove important in understanding the disease pattern and the complex functions of the brain.