Regulation of photoreceptor neurotransmission.

光感受器神经传递的调节。

• 批准号: 6518517
• 负责人: WALLACE B THORESON
• 金额: $ 24.93万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-01 至 2004-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6518517
• 关键词: Urodela; calcium channel; calcium indicator; calcium ion; chlorine; cone cell; electrophysiology; horizontal cell; light adaptations; neural transmission; retinal bipolar neuron; rod cell; second messengers; synapses; visual photoreceptor; voltage /patch clamp

DESCRIPTION (provided by applicant): The long-term goal of this project is to understand the mechanisms that control neurotransmission from rods and cones. Release of the excitatory neurotransmitter L-glutamate from photoreceptors is regulated by the activity of L-type Ca2+ channels. In the physiological voltage range, there appears to be a linear relationship between the influx of Ca2+ through these channels and the release of glutamate at the photoreceptor synapse. This linearity differs from the non-linear relationship found at most other synapses. One aim of this application is to use electrophysiological (capacitance monitoring and whole cell patch clamp recording) techniques, photolysis of caged Ca2+, and Ca2+ imaging techniques to examine the Ca2+ dependence of release from larval tiger salamander photoreceptors. One way in which a linear relationship between Ca2+ influx and release might arise is if vesicular exocytosis is initiated by the binding of only a single Ca2+ ion. If the binding of multiple Ca2+ ions is required to initiate release, then linearity between ICa and release is likely to reflect the linear summation, accompanying activation of an increasing number of Ca2+ channels, of sparsely distributed release sites with non-overlapping Ca2+ microdomains. These two possibilities will be investigated. The existence of a large number of modulators that can alter the voltage dependence or amplitude of photoreceptor ICa appear to present a challenge for photoreceptors to maintain the stable level of ICa activation necessary for stable synaptic output. The second major aim of this application is to use whole cell patch clamp recording as well as Ca2+ and Cl- imaging techniques to test the relative contribution of three specific intrinsic modulatory mechanisms to stabilizing ICa activation in rod and cone photoreceptors: (1) Ca-dependent inactivation of ICa, (2) depletion of synaptic cleft Ca2+, and (3) activation of Ca2+-activated Cl- channels. In addition to their importance in normal vision, regulation of photoreceptor ICa, intracellular Ca2+ concentration, and glutamate release are also important in pathophysiology of the retina. For example, increased intracellular Ca2+ levels in rods and cones may contribute to photoreceptor degeneration, and increased glutamate release arising from enhanced activation of ICa can have excitotoxic consequences on post-synaptic neurons. Thus, understanding the intrinsic mechanisms in rods and cones that regulate ICa, intracellular Ca2+ levels, and synaptic transmission is important for understanding the physiology of both diseased and normal retina.

描述(申请人提供)：本项目的长期目标是 了解控制视杆细胞和视锥细胞神经传递的机制。 兴奋性神经递质L-谷氨酸从光感受器释放 受L型钙通道活性调节。在生理电压中 在范围内，钙离子的内流似乎与 通过这些通道和光感受器谷氨酸的释放 Synapse。这种线性关系最多不同于所发现的非线性关系 其他突触。这项应用的一个目的是使用电生理学 (电容监测和全细胞膜片钳记录)技术， 笼中钙离子的光解及检测钙离子的成像技术 老虎幼体光感受器释放的依赖性。一条路可以进去 钙离子内流和释放之间可能出现的线性关系是 囊泡的胞吐作用是由一个单一的钙离子结合引起的。如果 需要结合多个钙离子才能启动释放，然后 ICA和释放之间的线性可能反映线性求和， 伴随着越来越多的钙通道的激活，稀疏的 钙离子微区不重叠的分布释放部位。这两个 将对可能性进行调查。 存在大量可以改变电压的调制器 光感受器ICA的依赖性或波幅似乎对 光感受器维持稳定的ICA激活水平 稳定的突触输出。此应用程序的第二个主要目标是使用 全细胞膜片钳记录以及钙离子和氯离子成像技术 检验三种特定的内在调节的相对贡献 稳定视杆细胞和视锥细胞ICA激活的机制：(1) 钙依赖的ICA失活，(2)突触间隙钙离子耗竭，和(3) 激活钙激活的氯离子通道。除了它们在以下方面的重要性 正常视力、光感受器ICA、细胞内钙离子的调节 浓度和谷氨酸的释放也是重要的病理生理学。 视网膜。例如，视杆细胞和视锥细胞内钙离子水平升高 可能导致光感受器退化，增加谷氨酸释放 由增强激活的ICA产生的可对 突触后神经元。因此，了解杆和杆的内在机制 调节ICA、细胞内钙离子水平和突触传递的锥体 对于理解疾病和正常的生理学都很重要 视网膜。