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MOLECULAR MECHANISM OF HYPERPOLARIZATION OF ON-BIPOLAR CELLS IN RETINA

视网膜双极细胞超极化的分子机制

基本信息

批准号：
05454634
负责人：
TSUDA Motoyuki
金额：
$ 4.16万
依托单位：
HIMEJI INSTITUTE OF TECHNOLOGY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454634/
关键词：
RETINA GULTAMATE RECEPTOR SECOND NEURON HYPERPOLARIZAION BIPOLAR CELL G-PROTEIN SYNAPSE RECEPTOR

项目摘要

Light reduce the release of glutamate from photoreceptor cell, resulting in opening of cation channels on on-bipolar cell and subsequent depolarization of the cell. In this respect, retinal onbipolar cell is a novel neuron which hyperpolarizes on contact with neurotransmitter molecules. Electrophysiological studies showed that cGMP act as the second messenger mediating the action of glutamate through the G protein that striking similarities to transduction in photoreceptors. In order to elucidate molecular mechanism of hyperpolarization of on-bipolar cell, we studied signal coupling proteins of on-bipolar cell in bovine retina.GTP-binding protein (G protein) linking to metabotropic glutamate receptor of bovine retinal on-bipolar cell was studied by use of pharmacologically selective ligands, 2-amino-4-phosphonobutyric acid (APB) on bacteria toxin-catalyzed ADP-ribosylation and GTP S-binding. In contrast to the electrophysiological finding reported, G-protein coupling to APB-sensitive glutamate receptor served as a substrate for pertussis toxin but did not for cholera toxin. Several glutamate analogues effective on on-bipolar cell, as well as APB,increased GTP S binding to retinal membranes devoid of rod outer segments. The enhancement of GTP S binding by APB was completely abolished when the membranes were pretreated with pertussis toxin and NAD.These results suggest that, in retinal on-bipolar cell, the G-protein which couples metabotropic glutamate receptor to hyperpolarizing response of the cell is sensitive to pertussis toxin.

光减少了感光细胞谷氨酸的释放，导致双极细胞上阳离子通道的开放和随后的细胞去极化。在这方面，视网膜双极细胞是一种新的神经元，超极化接触神经递质分子。电生理学研究表明，cGMP作为第二信使通过G蛋白介导谷氨酸的作用，这与光感受器中的转导有惊人的相似之处。为了阐明非双极细胞超极化的分子机制，我们研究了牛视网膜非双极细胞的信号偶联蛋白，并以细菌毒素催化的ADP核糖基化反应和GTP S结合反应为底物，研究了牛视网膜非双极细胞代谢型谷氨酸受体的GTP结合蛋白（G蛋白）。在相反的电生理发现报告，G-蛋白偶联APB敏感的谷氨酸受体作为百日咳毒素的底物，但没有霍乱毒素。几种对双极细胞有效的谷氨酸类似物以及APB增加了GTP S与缺乏视杆细胞外节的视网膜膜的结合。经百日咳毒素和NAD预处理后，APB对GTP S结合的增强作用被完全消除。这些结果表明，在视网膜双极细胞中，将代谢型谷氨酸受体偶联到细胞超极化反应的G蛋白对百日咳毒素敏感。