PHARMACOLOGY AND PHYSIOLOGY OF RETINAL GANGLION CELLS

视网膜神经节细胞的药理学和生理学

• 批准号: 2162019
• 负责人: ANDREW T ISHIDA
• 金额: $ 20.94万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2162019
• 关键词: G protein; GABA receptor; acetylcholine; action potentials; alternatives to animals in research; calcium flux; chloride channels; cholinergic receptors; eye pharmacology; gamma aminobutyrate; goldfish; in situ hybridization; neural inhibition; neuroanatomy; neuronal transport; neuropharmacology; neurophysiology; phosphodiesterases; potassium channel; protein kinase; retinal ganglion; synapses; tissue /cell culture; voltage /patch clamp

We are asking for support to continue our analysis of the electrophysiological and pharmacological properties of retinal ganglion cells. The long-term goal of this research is to determine how electrical signals in retinal ganglion cells are controlled before being sent to the brain. The proposed experiments will test mechanisms of ion channel regulation and action potential inhibition in retinal ganglion cells of adult goldfish. The specific aims of this work are: (1) to examine whether multiple gamma-aminobutyric acid receptors (termed GABAA and GABAB function independently of each other - i.e., whether each type of GABA receptor can inhibit ganglion cells, and whether activation of each type of GABA receptor influences function of the other. (2) to map receptors for acetylcholine (ACh) and GABA across ganglion cell dendrites and somata, and test whether ACh and GABA receptors function independently of each other. (3) to examine whether and how GTP-binding proteins, protein kinases, phosphodiesterases and intracellular messengers mediate or influence GABAA, GABAB, and ACh receptors and associated ion channels in retinal ganglion cells. (4) to assess the effect of intracellular Ca2+ levels on ion channels in ganglion cells, and characterize ion channels which establish intracellular Ca2+ levels. Ganglion cells will be identified by retrograde labeling or by morphological features, and studied with patch-clamp and immunocytochemistry in vitro in primary cell cultures, in situ in tangentially microdissected pieces of living retina, and in cryostat sections. Because the receptors and channels we propose to study exhibit basic similarities in all vertebrate classes, results of the proposed experiments are expected to apply to visual systems in general. Because inhibitory and excitatory synaptic input to retinal ganglion cells enables our eyes to encode size and motion of objects and edges, the work we propose here will contribute to a fuller understanding of critical visual processes.

我们要求支持继续我们的分析 视网膜神经节的电生理和药理特性 细胞。这项研究的长期目标是确定电气如何 视网膜神经节细胞中的信号在发送到 脑。提出的实验将测试离子通道的机制 调节和动作电位抑制在视网膜神经节细胞的 成人金鱼。这项工作的具体目的是： （1）检查多种γ-氨基丁酸受体（称为称为 GABAA和GABAB彼此独立地发挥作用 - 即是否 GABA受体的类型可以抑制神经节细胞，以及是否激活 每种类型的GABA受体都会影响对方的功能。 （2）跨神经节细胞绘制乙酰胆碱（ACH）和GABA的受体 树突和索马塔，并测试ACH和GABA受体是否功能 彼此独立。 （3）检查GTP结合蛋白，蛋白激酶是否以及如何 磷酸二酯酶和细胞内信使介导或影响 视网膜中的GABAA，GABAB和ACH受体以及相关的离子通道 神经节细胞。 （4）评估细胞内Ca2+水平对离子通道的影响 神经节细胞，并表征建立的离子通道 细胞内Ca2+水平。 神经节细胞将通过逆行标记或通过 形态学特征，并使用斑块夹和研究 原代细胞培养物的体外免疫细胞化学，原位 切向微切除的活性视网膜和低温恒温器 部分。因为我们建议研究展览的受体和通道 所有脊椎动物类别的基本相似性，提议的结果 预计实验通常适用于视觉系统。因为 对视网膜神经节细胞的抑制性和兴奋性突触输入可实现 我们的眼睛要编码物体和边缘的大小和运动，这是我们的工作 在这里提出的建议将有助于对关键视觉的更深入了解 过程。