QUANTAL EVENTS IN VISUAL TRANSDUCTION

视觉传导中的量子事件

• 批准号: 2161536
• 负责人: DAVID W CORSON
• 金额: $ 12.39万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-01 至 1999-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2161536
• 关键词: Rana; Urodela; Xenopus; active transport; cell membrane; chemical binding; chemical structure function; electromagnetic radiation; lipid transport; mathematical model; microspectrophotometry; molecular site; nutrition related tag; photoactivation; photostimulus; retinal adaptation; retinaldehyde; retinoids; rhodopsin; toad; transducin; visual photoreceptor; visual phototransduction

The quantal response to a single photon is the elemental event in vision. In rods, this discrete electrical event results from activation of an enzyme cascade that closes hundreds of channels in the plasma membrane. Absorption of a photon normally initiates the process of photoexcitation by isomerization of the chromophore retinal from 11-cis to the all-trans configuration within the visual pigment, rhodopsin. After excitation, all- trans retinal is released from the apoprotein opsin, and ultimately replaced with fresh 11-cis retinal supplied by the pigment epithelium. The size and shape of the quantal response are governed by l) the intramolecular events which result in formation of Metarhodopsin II and the exposure of a catalytic binding site for transducin, a GTP-binding protein, 2) deactivation of Metarhodopsin II by phosphorylation of the carboxy terminus and capping by arrestin, 3) nearby molecules of photoactivated rhodopsin that produce background adaptation, 4) nearby molecules of opsin that produce opsin desensitization and 5) the availability of 11-cis retinal to convert opsin to its inactive rhodopsin configuration. The longterm objective of this investigation is to determine the mechanism(s) of retinoid uptake into photoreceptors and to gain a molecular explanation of the influence of the retinoids in the mechanisms of excitation and adaptation. As outlined in the progress report, work initiated in this laboratory has demonstrated that it is possible to manipulate excitation, adaptation and retinoid uptake with analogues of retinal. The Specific Aims of this proposal are to exploit these observations with an analysis of the physiological activities of selected analogues of retinal in intact cells. To this end, we propose: l) to determine the minimum structural requirements of retinal for the relief of opsin desensitization and for the control of excitation in rods & cones, 2) to identify the biochemical pathway responsible for opsin desensitization. 3) to determine the mechanism of retinoid uptake in rods and cones. The proposed work is addressed to program priorities of the NEI panel on Retinal and Choroidal Diseases. The work addresses fundamental mechanisms of receptor activation and desensitization with health ramifications relating to the efficacy of drugs and to the anomalies of pigment activation and dark adaptation associated with retinitis pigmentosa.

对单个光子的数量响应是视觉中的元素事件。 在杆中，该离散的电气事件是由于激活 在质膜中关闭数百个通道的酶级联。 光子的吸收通常启动光激发的过程 通过异构化发色团视网膜从11-cis到全型 视觉色素内的构型Rhodopsin。激发后， 反式视网膜是从载脂蛋白Opsin释放的，最终是 取而代之的是颜料上皮提供的新鲜的11盘视网膜。这 数量响应的大小和形状由l）控制 分子内事件导致形成元视丁蛋白II和 催化结合位点的传播drodducin，一种GTP结合 蛋白质，2）通过磷酸化磷酸化元素II 羧基末端和被逮捕的封盖，3）附近的分子 产生背景适应的光活化的视紫红质，4）附近 产生Opsin脱敏的Opsin分子，5） 11盘视网膜的可用性将Opsin转换为其无活跃的视紫红蛋白 配置。 这项调查的长期目标是确定 类视黄素摄取对感光体的机理并获得 分子解释性类维生素的影响在机理中 激发和适应。如进度报告中概述的 在该实验室发起的已经表明，有可能 操纵激发，适应和类视黄素的吸收 视网膜。 该提案的具体目的是利用这些 通过分析选定的生理活性的观察 视网膜完整细胞中的类似物。为此，我们提出：l） 确定视网膜的最低结构要求 Opsin脱敏和控制杆和锥体激发的控制， 2）确定负责Opsin的生化途径 脱敏。 3）确定杆中类视黄素吸收的机理 和锥。 拟议的工作涉及NEI面板的计划优先级 视网膜和脉络膜疾病。工作涉及基本机制 受体激活和脱敏的健康影响 与药物的功效和色素异常有关 与色素性视网膜炎相关的激活和黑暗适应性。