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Function, structure and regulation of two kinds of Cl^- channels involved in gastric acid secretion

两种参与胃酸分泌的Cl^-通道的功能、结构及调控

基本信息

批准号：
02454115
负责人：
TAKEGUCHI Noriaki
金额：
$ 2.82万
依托单位：
Toyama Medical and Pharmaceutical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-02454115/
关键词：
Cl^- channel proton pump gastric acid secretion H^+, K^+-ATPase Cl^-チャネル

项目摘要

Two different Cl- channels which are present in the basolateral and apical membranes of acid secreting cells are studied here. Usually, cell membrane potentials are determined by equilibrium potential to K+ : that is, K+ conductance determines the potential. But in the rabbit parietal cell, the membrane potential was found to be determined by Cl- channel in the basolateral membrane. The single Cl- channel conductance was found to be only 0.3 pS from an experiment of patch clamp-ensemble noise analysis. The Cl- channel was activated by arachidonic acid (AA) and prostaglandin E2 (PG), and inhibited by GTP S. In other types of cells, AA and PG are known to inhibit Cl- channel and GTP S activates the channel, which is in contrary to what found for the present gastric Cl- channel. Regulation of the cell membrane potential via the Cl- Channd engages in cytoprotection against strong gastric acid and stress.Isolation of parietal cells results in formation of occluded canaliculus and the apical membrane is not able to be reached from the cell surface by a micropipette. We found that oxyntic cells isolated from red belly newt expose both the basolateral and apical membranes to the bath medium from an experiment in which acid-activated proton pump inhibitor, methoxy E3810, was poured on the surface of the isolated cell, the S-S cross-linked inhibitor was irradiated with ultraviolet light, and the increase in the fluorescence was measured. The distribution of the pump was obtained from the image fluorescence analysis of single cells. Using the oxyntic cells we succeeded to detect the apical Cl- channel although more detailed study is necessary to characterize the apical Cl- channel.

两种不同的氯离子通道，这是目前在基底和顶端膜的泌酸细胞在这里进行了研究。通常，细胞膜电位由K+的平衡电位决定：即K+电导决定电位。而在兔壁细胞中，膜电位则由基底外侧膜上的Cl-通道决定。单个Cl-通道电导被发现是只有0.3 pS的实验膜片钳系综噪声分析。花生四烯酸（AA）和前列腺素E_2（PG）对Cl-通道有激活作用，而GTP S则对Cl-通道有抑制作用。在其他类型的细胞中，已知AA和PG抑制Cl-通道，GTP S激活该通道，这与目前胃Cl-通道的发现相反。细胞膜电位的调节通过Cl-β d参与细胞保护以对抗强胃酸和应激。壁细胞的分离导致形成封闭的小管，并且顶膜不能通过微量移液器从细胞表面到达。我们发现，从红腹蝾螈分离的泌酸细胞暴露的基底外侧和顶端膜浴介质从实验中，酸活化的质子泵抑制剂，甲氧基E3810，倒在分离的细胞的表面上，S-S交联的抑制剂用紫外线照射，并测量荧光的增加。从单细胞的图像荧光分析获得泵的分布。使用泌酸细胞，我们成功地检测到顶端的Cl-通道，虽然更详细的研究是必要的，以表征顶端的Cl-通道。