ROLES OF CGMP-GATED CHANNELS IN RETINAL BIPOLAR NEURONS

CGMP 门控通道在视网膜双极神经元中的作用

• 批准号: 6226882
• 负责人: GARY G MATTHEWS
• 金额: $ 32.64万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6226882
• 关键词: alternatives to animals in research; cGMP dependent protein kinase; cyclic GMP; electrophysiology; flash photolysis; glutamate receptor; goldfish; image processing; immunocytochemistry; in situ hybridization; neural information processing; phosphodiesterases; polymerase chain reaction; retinal bipolar neuron; synapses; visual photoreceptor; visual phototransduction; voltage gated channel

DESCRIPTION (Applicant's Description): The goal of this project is to understand the molecular mechanisms of neurotransmitter responses in retinal bipolar neurons, with a focus on the roles of cyclic nucleotide-gated (CNG) channels. Visual signals from the photoreceptors are funneled to the rest of the brain exclusively through bipolar neurons, which therefore occupy a central position in retinal information processing. The separation of visual information into the ON pathway (in which cells depolarize in response to light) and the OFF pathway (in which cells hyperpolarize in response to light) occurs in bipolar neurons, at the first synapse in the visual system. The proposed research project will explore the cellular mechanisms that generate the ON pathway at the synapse between photoreceptor cells and ON bipolar neurons. At this synapse, glutamate released from the photoreceptor hyperpolarizes ON bipolar cells by activating a transduction cascade culminating in closure of cation channels. These cation channels may be members of the family of CNG channels, which open when cyclic GMP binds directly to the intracellular portion of the channel. A combination of electrical recording and fluorescence imaging techniques will be used to establish the role of CNG channels and cyclic GMP in the glutamate response of ON bipolar cells. Other potential roles of CNG channels will also be explored, such as modulation of neurotransmitter release in the synaptic terminal of the bipolar cell. Molecular biological techniques will be used to identify and characterize the CNG channel subtypes expressed in bipolar neurons. From amino acid sequences derived from complementary DNA encoding CNG channel subtypes, selective antibodies will be produced that can be used to localize the channel subtypes in isolated cells and retinal tissue. Biophysical characterization of CNG channel subtypes found in bipolar neurons will be carried out both in bipolar neurons and in cells transfected with full-length complementary DNA encoding a specific channel subtype. The proposed experiments will provide new information about the synaptic responses of an important class of retinal neurons and will specify physiological roles for specific types of CNG channels expressed in these neurons. Because cyclic nucleotide-gated channels are found in a variety of cell types throughout the nervous system, the results of the proposed project will also have general implications for cellular communication in the other parts of the brain.

描述（申请人的描述）：本项目的目标是 了解视网膜神经递质反应的分子机制， 双极神经元，重点是环核苷酸门控（CNG）的作用 渠道来自光感受器的视觉信号通过漏斗状通道传递到 大脑只通过双极神经元，因此占据了中央 在视网膜信息处理中的地位。视觉的分离 信息进入ON途径（其中细胞响应于 光）和OFF途径（其中细胞对光作出反应而过度增殖） 发生在双极神经元，在视觉系统的第一个突触。的 拟议的研究项目将探索细胞机制，产生 光感受器细胞和ON双极之间突触处的ON通路 神经元在这个突触上，感光细胞释放的谷氨酸 通过激活转导级联使ON双极细胞超极化 最终导致阳离子通道的关闭。这些阳离子通道可能是 CNG通道家族，当环GMP直接结合到 通道的细胞内部分。电子记录和 荧光成像技术将用于确定CNG的作用 通道和环GMP在ON双极细胞谷氨酸反应中的作用。其他 CNG通道的潜在作用也将探讨，如调制 双极细胞突触末端的神经递质释放。 分子生物学技术将用于鉴定和表征 CNG通道亚型在双极神经元中表达。从氨基酸序列 来源于编码CNG通道亚型的互补DNA，选择性 将产生可用于定位通道亚型的抗体 在分离的细胞和视网膜组织中。CNG的生物物理特性 在双极神经元中发现的通道亚型将在双极神经元和双极神经元中进行。 在神经元和用全长互补DNA转染的细胞中， 特定通道子类型。拟议中的实验将提供新的信息 关于一类重要的视网膜神经元的突触反应， 特定类型CNG通道的特定生理作用， 这些神经元。因为环核苷酸门控通道存在于多种 整个神经系统的细胞类型，结果的建议， 该项目还将对全球范围内的蜂窝通信产生普遍影响。 大脑的其他部分。