PHARMACOLOGY & PHYSIOLOGY OF RETINAL GANGLION CELLS

药理

• 批准号: 6635610
• 负责人: ANDREW T ISHIDA
• 金额: $ 29.7万
• 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 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6635610
• 关键词: G protein; GABA receptor; action potentials; alternatives to animals in research; calcium flux; chloride channels; cholinergic receptors; eye pharmacology; goldfish; in situ hybridization; laboratory rat; neural inhibition; neuronal transport; neuropharmacology; neurophysiology; potassium channel; protein kinase; retinal ganglion; tissue /cell culture; voltage /patch clamp; voltage gated channel

DESCRIPTION (Verbatim from applicant's abstract): The major objective of this application is to understand how retinal ganglion cells function by using electrophysiology and pharmacology to identify distinct ion currents that depolarize ganglion cells to action potential threshold; identify ion current properties that modulate repetitive action potential firing in these cells; and determine whether these properties are controlled over slow time-scales by cytoplasmic messengers. These experiments stem directly from measurements and calculations published during the previous funding period. The hypothesis that low-threshold Na+, Ca2+ and mixed-cation currents produce "non-synaptic excitatory potentials" in retinal ganglion cells will be tested by investigating whether low-threshold ion currents depolarize ganglion cells to action potential threshold, and whether they do so separately or sequentially. The hypothesis that slow changes in retinal ganglion cell excitability results from modulation of low-threshold ion currents by neurotransmitters will be tested by investigating whether modulatory neurotransmitters (dopamine) alter spike frequency by modulating the amplitude, gating kinetics, and/or voltage-sensitivity of Na+ currents, low-threshold Ca2+ currents and/or Ih currents. The last hypothesis, that mammalian retinal ganglion cells' excitability is influenced by low-threshold ion currents similar to those found in fish, will be tested by comparing the amplitude and kinetics of fish and mammalian ganglion cell ion currents, and by determining the ion currents responsible for the previous reports of voltage-rectification, and of tetrodotoxin-induced hyperpolarization in mammalian preparations. These experiments will be performed with whole-cell patch-clamp methods to voltage-clamp and current-clamp goldfish retinal ganglion cells. Recordings will be made from freshly dissociated ganglion cells and ganglion cells in retinal slices.

描述（逐字研究来自申请人的摘要）：这是其中的主要目的 应用是了解视网膜神经节细胞如何通过使用 电生理学和药理学，以识别不同的离子电流 将神经节细胞去极化阈值；识别离子电流 调节这些细胞中重复作用电势的特性；和 确定这些属性是否通过缓慢的时间尺度控制 细胞质使者。这些实验直接源于测量和 在上一个资金期间发布的计算。假设是 低阈值Na+，Ca2+和混合燃料电流产生非突触 视网膜神经节细胞中的兴奋电位将通过 调查低阈值离子电流是否将神经节细胞去极化 动作电势阈值，以及它们是单独还是顺序进行的。 视网膜神经节细胞兴奋性结果缓慢变化的假设 通过神经递质对低阈值离子电流的调节将是 通过研究调节性神经递质（多巴胺）测试 通过调节振幅，门控动力学和/或 Na+电流，低阈值Ca2+电流和/或IH的电压敏感性 电流。最后一个假设是哺乳动物视网膜神经节细胞的 兴奋性受到低阈值离子电流的影响 在鱼类中，将通过比较鱼类的幅度和动力学来测试 哺乳动物神经节细胞离子电流，并通过确定离子电流 负责先前的电压分解报告和 四毒素诱导的哺乳动物制剂中的超极化。 这些实验将使用全细胞斑块钳方法进行 电压钳和电流钳金鱼视网膜神经节细胞。录音 将由新鲜分离的神经节细胞和神经节细胞制成 视网膜切片。