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Evaluation of agonist selectivity with glutamate receptor ion channel sensors

谷氨酸受体离子通道传感器激动剂选择性的评估

基本信息

批准号：
10440219
负责人：
SUGWARA Masao
金额：
$ 5.7万
依托单位：
Nihon University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

1. The magnitude of agonist-induced integrated single-channel current, corresponding to the number of ions passed through a single glutamate receptor (GluR) channel in bilayer lipid membranes (BLMs) during a unit time, was quanrified as a new measure of agonist selectivity. The agonist selectivity among the typical agonists, NMDA, L-glutamate and L-CCG-IC, in terms of the integrated single-channel current was in the order of L-CCG-IV>L-glutamate>NMDA.2. To quantify the ion-permeation ability of the recombinant ε1-4/ζ1 N-methyl-D-aspartate (NMDA) channels activated by agonists, the magnitude of agonist-induced integrated single-channel currents for the ε1-4/ζ1 NMDA receptor channels in BLMs was evaluated. It was found that the magnitude of L-glutamate-induced integrated current depends on ε-subunit composition and the signal transduction abilty of the ε1-4/ζ1 NMDA receptor is not parallel to its binding ability.3. The magnitude of Ca^<2+> release from GluR-incorporated liposomes, which was measured by a Ca^<2+> ion-selective electrode with a thin-layer mode, was proposed as a measure of agonist selectivity for NMDA receptor.4. A single-channel method for evaluating agonist selectivity in terms of the very number of Ca^<2+> ions passed through the ε4/ζ1 NMDA receptor ion channel in BLMs was proposed.

1. 激动剂诱导的积分单通道电流的大小，对应于单位时间内通过双层脂膜 (BLM) 中单个谷氨酸受体 (GluR) 通道的离子数量，被量化为激动剂选择性的新衡量标准。典型激动剂NMDA、L-谷氨酸和L-CCG-IC之间的激动选择性，就积分单通道电流而言，顺序为L-CCG-IV>L-谷氨酸>NMDA。2。为了量化激动剂激活的重组 ε1-4/z1 N-甲基-D-天冬氨酸 (NMDA) 通道的离子渗透能力，评估了 BLM 中 ε1-4/z1 NMDA 受体通道的激动剂诱导的集成单通道电流的大小。结果发现，L-谷氨酸诱导的积分电流的大小取决于ε亚基的组成，ε1-4/ζ1 NMDA受体的信号转导能力与其结合能力并不平行。 3．提出用薄层模式的Ca 2+ 离子选择性电极测量掺入GluR的脂质体中Ca 2+ 释放的量作为NMDA受体激动剂选择性的量度。4．提出了一种根据通过BLM中ε4/z1 NMDA受体离子通道的Ca ^ 2+ 离子数量来评估激动剂选择性的单通道方法。