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A study on the inactivation of voltage-gated potassium channels.

电压门控钾通道失活的研究。

基本信息

批准号：
09640810
负责人：
FURUKAWA Yasuo
金额：
$ 1.98万
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：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09640810/
关键词：
ion channels inactivation molecular mechanisms

项目摘要

Voltage-gated potassium channels are macromolecular pores, which permit the trans-membrane flux of potassium ions. Most potassium channels enter the inactivated states, which do not permit the permeation of ions. In this study, molecular mechanisms of the inactivation were examined on some cloned voltage-gated potassium channels (two Aplysia channels, aKvl.la & aKv5.1, and a rat channel, rKvl.4). aKvl.la and rKvl.4 are homologous channels, and both channels show a prominent inactivation called the accumulative inactivation. When the channel currents were examined in inside-out patches, however, these two channels showed a remarkable contrast ; the accumulative inactivation of aKvl.la was enhanced, while that of rKviL4 depressed. There are some evidence which suggest the involvement of pore structure in the accumulative inactivation, and indeed, in the pore region of the channels, 8 amino acids are different between aKvl.la and rKvl.4. Therefore, eight pore mutants of aKvl.la were made, and the effects of each mutation were examined in Xenopus oocyte expression system. The results suggest that the difference of the accumulative inactivation of aKvl.la and rKvl.4 is due to the different structure of the external mouth of the pore. To confirm the results in the channels that lack N-type inactivation, the amino-terminal deletion mutants of the eight mutants were made. The functional consequence of such deletion on the accumulative inactivation is currently under investigation. Because aKv5.1 lacks the inactivation at all, we are now trying to examine the chimera channels between aKvl.la and aKv5.1 to delineate the important domains for the inactivation.

电压门控钾通道是一种大分子孔，允许钾离子跨膜流动。大多数钾通道进入失活状态，不允许离子渗透。在这项研究中，在一些克隆的电压门控钾通道上检查了失活的分子机制（两个ARACINSIA通道，aKvl.la & aKv5.1，和大鼠通道，rKvl.4）。aKvl.la和rKvl.4是同源通道，并且两个通道都显示出被称为累积失活的显著失活。然而，当通道电流在由内而外的补丁检查，这两个通道表现出显着的对比;的累积失活的aKvl.la增强，而rKviL 4的抑制。有一些证据表明孔结构参与了累积失活，实际上，在通道的孔区域中，aKvl.la和rKvl.4之间有8个氨基酸不同。因此，制备了aKvl.la的8个孔突变体，并在非洲爪蟾卵母细胞表达系统中检测了每个突变体的效果。结果表明aKvl.la和rKvl.4累积失活的差异是由于孔的外口结构不同。为了确认缺乏N型失活的通道中的结果，制备了八种突变体的氨基末端缺失突变体。这种缺失对累积失活的功能后果目前正在调查中。由于aKv5.1完全缺乏失活，我们现在正试图检查aKvl.la和aKv5.1之间的嵌合体通道，以描绘失活的重要结构域。