CALCIUM AND ADAPTATION IN MAMMALIAN CONE PHOTORECEPTORS

钙与哺乳动物视锥光感受器的适应

• 批准号: 7638095
• 负责人: Vladimir Jivkov Kefalov
• 金额: $ 11.46万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7638095
• 关键词: Address; Calcium; Color Perception; Cyclic GMP; Darkness; Feedback; Guanylate Cyclase; Light; Light Adaptations; Mediating; Molecular; Mus; Phosphorylation; Photoreceptors; Phototransduction; Physiological; Play; Property; Protein Isoforms; Regulation; Resolution; Retinal Cone; Retinal Pigments; Role; Testing; Vertebrate Photoreceptors; Vision; guanylate cyclase activating protein; light intensity; photoactivation; public health relevance; recoverin protein; research study; retinal rods; rhodopsin kinase

DESCRIPTION (provided by applicant): Cone photoreceptors function under daylight conditions and are essential for color perception and vision with high temporal and spatial resolution. A remarkable feature of cones is their ability to remain functional in bright light which requires powerful adaptation mechanisms of their phototransduction cascade. In rods, light adaptation is mediated by calcium and the mechanisms by which reduction in calcium upon photo-activation modulates phototransduction are well understood. While photo-activation also triggers a decline in calcium in cones, the molecular mechanisms by which this exerts negative feedback on cone phototransduction are not known. The experiments described here will employ physiological studies from available genetically modified mice to investigate the mechanisms of modulation of the cone phototransduction cascade by calcium. Specifically, we will test the hypothesis that regulation of visual pigment phosphorylation by rhodopsin kinase via recoverin is a component of the calcium feedback in mouse cones and modulates their phototransduction in darkness and during light adaptation. We will also test the hypothesis that regulation of cGMP synthesis by guanylyl cyclase via Guanylyl Cyclase Activating Proteins (GCAPs) is a major component of the calcium feedback in mouse cones and modulates their phototransduction in darkness and during light adaptation. Together, these experiments will help us determine the mechanisms that allow cones to adapt to a very wide range of light intensities and remain functional throughout the day, even in bright light. PUBLIC HEALTH RELEVANCE: The experiments outlined in this proposal seek to establish the mechanisms that enable mammalian cones to function in bright light, an essential property for the photoreceptors that mediate daytime vision. These studies will help us understand the role of calcium in regulating mammalian cone function under normal and pathological conditions.

描述（由申请人提供）：视锥细胞在日光条件下发挥作用，对于具有高时间和空间分辨率的颜色感知和视觉至关重要。视锥细胞的一个显着特征是它们在强光下保持功能的能力，这需要其光转导级联的强大适应机制。在视杆细胞中，光适应是由钙介导的，并且光激活时钙的减少调节光转导的机制是众所周知的。虽然光激活也会引发视锥细胞中钙的减少，但其对视锥细胞光转导产生负反馈的分子机制尚不清楚。这里描述的实验将利用现有转基因小鼠的生理学研究来研究钙调节视锥细胞光转导级联的机制。具体来说，我们将测试以下假设：视紫红质激酶通过恢复蛋白调节视色素磷酸化是小鼠视锥细胞中钙反馈的一个组成部分，并在黑暗和光适应过程中调节其光转导。我们还将测试以下假设：鸟苷酸环化酶通过鸟苷酸环化酶激活蛋白 (GCAP) 调节 cGMP 合成是小鼠视锥细胞中钙反馈的主要组成部分，并在黑暗和光适应过程中调节其光转导。总之，这些实验将帮助我们确定使视锥细胞适应非常广泛的光强度并在一天中（即使在强光下）保持功能的机制。 公共健康相关性：本提案中概述的实验旨在建立使哺乳动物视锥细胞在强光下发挥作用的机制，这是介导白天视觉的光感受器的基本特性。这些研究将帮助我们了解钙在正常和病理条件下调节哺乳动物视锥细胞功能的作用。