The eag family of K+ channels in Drosophila and mammals
The eag family of K+ channels in Drosophila and mammals
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DOI：
10.1111/j.1749-6632.1999.tb11297.x
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发表时间：
1999-01-01
期刊：
影响因子：
--
通讯作者：
Titus, SA
中科院分区：
文献类型：
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作者：
Ganetzky, B;Robertson, GA;Titus, SA
eag 突变最初是在果蝇中根据其腿颤动表型发现的，它会导致运动神经元的重复放电和递质释放增强。编码的 EAG 多肽与电压门控 K+ 通道和环核苷酸门控阳离子通道均相关。同源性筛选鉴定出 eag 相关通道多肽家族，该家族从线虫到人类高度保守，包含三个亚家族：EAG、ELK 和 ERG。当在青蛙卵母细胞中表达时，EAG 通道表现为电压依赖性、向外整流 K+ 选择性通道。人类 eag 相关基因 (HERG) 的突变会导致心律失常，从而导致心室颤动和猝死。电生理学和药理学研究提供的证据表明，HERO 通道指定延迟整流器 I-Kr 的一种成分，该成分有助于心脏动作电位的复极相。脑组织中这些通道的表达也表明了 HERO 通道在神经元兴奋性中的重要作用。此外，果蝇 sei 突变体中 ERG 型通道的突变会导致与飞行运动通路中异常爆发活动相关的温度诱导的惊厥性癫痫发作。ELK 通道的体内功能尚未建立，但当这些通道在青蛙卵母细胞中表达时，它们表现出介于 EAG 和 ERG 型通道之间的特性。 Hk 编码的 K+ 通道 β 亚基与 EAG 在卵母细胞中的共表达显着增加了电流幅度，并且还影响这些电流的门控和调制。生化证据表明 EAG 和 BK 蛋白之间存在直接的物理相互作用。总体而言，这些研究强调了 K+ 通道 eag 家族的不同特性，这些特性可能在体内促进不同的功能。
Mutations of eag, first identified in Drosophila on the basis of their leg-shaking phenotype, cause repetitive firing and enhanced transmitter release in motor neurons. The encoded EAG polypeptide is related both to voltage-gated K+ channels and to cyclic nucleotide-gated cation channels. Homology screens identified a family of eag-related channel polypeptides, highly conserved from nematodes to humans, comprising three subfamilies: EAG, ELK, and ERG. When expressed in frog oocytes, EAG channels behave as voltage dependent, outwardly rectifying K+-selective channels. Mutations of the human eag-related gene (HERG) result, in a form of cardiac arrhythmia that can lead to ventricular fibrillation and sudden death. Electrophysiological and pharmacological studies have provided evidence that HERO channels specify one component of the delayed rectifier, I-Kr, that contributes to the repolarization phase of cardiac action potentials. An important role for HERO channels in neuronal excitability is also suggested by the expression of these channels in brain tissue, Moreover, mutations of ERG-type channels in the Drosophila sei mutant cause temperature-induced convulsive seizures associated with aberrant bursting activity in the flight motor pathway, The in vivo function of ELK channels has not yet been established, but when these channels are expressed in frog oocytes, they display properties intermediate between those of EAG- and ERG-type channels. Coexpression of the K+-channel beta subunit encoded by Hk with EAG in oocytes dramatically increases current amplitude and also affects the gating and modulation of these currents. Biochemical evidence indicates a direct physical interaction between EAG and BK proteins. Overall, these studies highlight the diverse properties of the eag family of K+ channels, which are likely to subserve diverse functions in vivo.