Molecular and functional characterization of voltage-gated sodium channel variants from Drosophila melanogaster
Molecular and functional characterization of voltage-gated sodium channel variants from Drosophila melanogaster
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DOI：
10.1016/j.ibmb.2008.01.003
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发表时间：
2008-05-01
影响因子：
3.8
通讯作者：
Dong, Ke
中科院分区：
文献类型：
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作者：
Olson, Rachel O'Donnell;Liu, Zhiqi;Dong, Ke
DmNa(V)(前身为PARA)是果蝇中唯一的钠通道基因，已被证明是广泛的选择性剪接和RNA编辑。然而，这些转录后修饰的功能后果还没有被很好地理解。在本研究中，我们分离了的全长DmNa(V)基因克隆。根据11个选择性外显子的使用情况，无性系可分为29个剪接类型。当在非洲爪哇卵母细胞中表达时，33个DmNa(V)变异体产生了足够大的钠电流，足以进行功能表征。在这些变异体中，DmNa(V)5-1和DmNa(V)7-1通道在最大超极化电位激活，而DmNa(V)1-6和DmNa(V)19通道在最去极化膜电位激活。我们在DmNa(V)5-1中发现了一个A-to-I编辑事件，该事件负责其独特的低电压依赖激活。DmNav变异体表现出的广泛的电压依赖性门控特性为未来的研究提供了丰富的资源，以确定DmNav在调节昆虫钠通道门控、药理学和神经元兴奋性中的作用。(C)2008爱思唯尔有限公司。保留所有权利。
Extensive alternative splicing and RNA editing have been documented for the transcript of DmNa(V) (formerly para), the sole sodium channel gene in Drosophila melanogaster. However, the functional consequences of these post-transcriptional modifications are not well understood. In this study we isolated 64 full-length DmNa(V) cDNA clones from D. melanogaster adults. Based on the usage of 11 alternative exons, 64 clones could be grouped into 29 splice types. When expressed in Xenopus oocytes, 33 DmNa(V) variants generated sodium currents large enough for functional characterization. Among these variants, DmNa(V)5-1 and DmNa(V)7-1 channels activated at the most hyperpolarizing potentials, whereas DmNa(V)1-6 and DmNa(V)19 channels activated at the most depolarizing membrane potentials. We identified an A-to-I editing event in DmNa(V)5-1 that is responsible for its uniquely low-voltage-dependent activation. The wide range of voltage dependence of gating properties exhibited by DmNav variants represents a rich resource for future studies to determine the role of DmNav in regulating sodium channel gating, pharmacology, and neuronal excitability in insects. (C) 2008 Elsevier Ltd. All rights reserved.