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A study on the structure-function relationship and the physiological function of the peptide-gated sodium channel

肽门控钠通道的结构与功能关系及生理功能研究

基本信息

批准号：
18570071
负责人：
FURUKAWA Yasuo
金额：
$ 2.57万
依托单位：
Hiroshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18570071/
关键词：
ion channel peptide structure-function relationship

项目摘要

The aim of this study is to explore structural basis of the functional properties of FMRFamide-gated Ha+channel, which is the only peptide-gated sodlium channel who primary structure is known. To this end, we examined Aplysia FMRFamide-gated Na+ channel in Xenopus oocytes. Both the wild-type as well as the mutated channels made by PCR were expressed in Xenopus oocytes, and their functions were analyzed under voltage clamp. Main results obtained are as follows.(1) Steady state current-voltage relationship of FMRFamide-gated Na^+ channel showed an inward rectification. It was fauna that the rectification was due to the unequal Na+ concentration in inside and outside of the cell.(2) FMRFamide-gated Na+ channel currents were potentiated in a solution containing high Mg^<2+>, and depressed in a solution containing high Ca^<2+>. In addition to the pore block by divalent cations, the gating efficacy of the channel seemed to be modified by divalent cations.(3) The opening of FMRFamide-gated Na+ channel was promoted in hyperpolarized membrane potential, and the effect of membrane potential was also modified by divalent cations.(4) Many of the actions of divalent cations were either abolished or depressed in a mutant channel, D552N, in which aspartate in the position 552 (Asp^<552>) was replaced with asparagine.Based on these results, we propose that Asp^<552> is involved in a binding site of divalent cations, and that the site is essential for physiological function of FMRFamide-gated Na^+ channel. We are currently carrying out a project focusing on the function of Asp^<552> of FMRFamide-gated Na^+ channel.

FMRFamide门控的Ha+通道是目前已知的唯一一级结构的肽门控钠离子通道，本研究旨在探讨其功能特性的结构基础。为此，我们研究了非洲爪蟾卵母细胞的FMRFamide门控Na+通道。野生型以及突变的通道通过PCR在非洲爪蟾卵母细胞中表达，并在电压钳下分析其功能。主要结果如下。(1)FMRFamide门控Na^+通道稳态电流-电压关系呈内向整流。细胞内外Na+浓度的不均衡是导致细胞发生整流的主要原因。(2)FMRFamide门控的Na+通道电流在含高Mg^<2+>的溶液中增强，在含高Ca^<2+>的溶液中抑制。除了二价阳离子的孔阻塞之外，通道的门控功效似乎被二价阳离子修饰。(3)在超极化膜电位条件下，FMRFamide门控Na+通道开放被促进，二价阳离子对膜电位的影响也被修饰。(4)D552 N通道中552位天冬氨酸（Asp^）被天冬酰胺取代，二价阳离子的许多作用被取消或抑制<552>，据此我们推测Asp^<552>参与了二价阳离子的结合位点，该位点是FMRFamide门控Na^+通道生理功能所必需的。我们目前正在开展一个项目，重点是研究<552>FmRFamide门控Na^+通道中Asp^的功能。