Retinal Inhibitory Glycine Receptors

视网膜抑制性甘氨酸受体

• 批准号: 7281193
• 负责人: MALCOLM M SLAUGHTER
• 金额: $ 38.11万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7281193
• 关键词: Retinal; Inhibitory; Glycine; Receptors

DESCRIPTION (provided by applicant): The glycine receptor is a key inhibitory receptor in the retinal inner plexiform layer. It is found in ~ 40% of amacrine cells. Almost all retinal neurons express glycine receptors. Although glycine performs a number of roles in retina, there has not been a description of the different glycine receptors that may exist. This is in contrast to the two other main fast transmitters in retina, GABA and glutamate. Receptor subtypes for both of these neurotransmitters have been identified, extensively described, and shown to play key, distinct roles in retinal physiology. It is evident that the complexity of synaptic communication in retina is largely due to the diversity of GABA and glutamate receptor subtypes. The same level of complexity is not evident at the glycinergic synapse. A major limitation is that there is very little information about glycine receptor subtypes and poor tools to investigate it. The governing hypothesis of this proposal is that there are multiple glycine receptors in retina. The research plan will be to address the functional and pharmacological differences between glycine receptors in retina, correlating this with the properties of glycine subunits. It is known that at least three types of glycine receptor alpha subunit are expressed in retina and they have different distributions. This implies that there are functional differences between the subunits, warranting the anatomical segregation. This study's long term goal is to define the properties of glycine receptor subtypes as they relate to the function of the synapse and the physiology of vision. One motivation for this study is our finding that there are fast and slow glycine currents in ganglion cells, that these currents have different pharmacological properties, and that they are differentially regulated by second messenger pathways. This suggests that glycine receptor subtypes exist and that their properties are important in specific retinal functions. A first step in understanding glycine receptor diversity is to develop the tools to identify and characterize glycine receptor subtypes. This proposal will use biophysical, pharmacological, and molecular approaches to develop these tools. Two specific aims are to find agonists and antagonists that can distinguish between glycine receptor subtypes. Another is to characterize GABA receptor antagonists which interact with the glycine receptor. These specific aims are a necessary first step in unraveling inhibitory synapses in retina.

描述（申请人提供）：甘氨酸受体是视网膜内丛状层中的关键抑制性受体。它存在于约 40% 的无长突细胞中。几乎所有视网膜神经元都表达甘氨酸受体。尽管甘氨酸在视网膜中发挥多种作用，但尚未描述可能存在的不同甘氨酸受体。这与视网膜中另外两种主要的快速递质 GABA 和谷氨酸形成鲜明对比。这两种神经递质的受体亚型已被鉴定、广泛描述，并显示在视网膜生理学中发挥着关键、独特的作用。显然，视网膜突触通讯的复杂性很大程度上归因于 GABA 和谷氨酸受体亚型的多样性。甘氨酸突触具有相同程度的复杂性并不明显。一个主要的限制是关于甘氨酸受体亚型的信息非常少，而且研究它的工具也很差。该提议的主导假设是视网膜中有多种甘氨酸受体。该研究计划将解决视网膜甘氨酸受体之间的功能和药理学差异，并将其与甘氨酸亚基的特性联系起来。已知至少三种类型的甘氨酸受体α亚基在视网膜中表达，并且它们具有不同的分布。这意味着亚基之间存在功能差异，保证了解剖学上的分离。这项研究的长期目标是确定甘氨酸受体亚型的特性，因为它们与突触功能和视觉生理学相关。这项研究的动机之一是我们发现神经节细胞中存在快速和慢速甘氨酸电流，这些电流具有不同的药理学特性，并且它们受到第二信使途径的差异调节。这表明甘氨酸受体亚型的存在，并且它们的特性对于特定的视网膜功能很重要。了解甘氨酸受体多样性的第一步是开发识别和表征甘氨酸受体亚型的工具。该提案将使用生物物理、药理学和分子方法来开发这些工具。两个具体目标是寻找能够区分甘氨酸受体亚型的激动剂和拮抗剂。另一个是表征与甘氨酸受体相互作用的 GABA 受体拮抗剂。这些具体目标是解开视网膜抑制性突触必要的第一步。