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）：锥形光感受器在日光条件下起作用，对于具有高时空和空间分辨率的颜色感知和视觉至关重要。锥体的一个显着特征是它们在明亮的光线下保持功能的能力，这需要其光转导级联的强大适应机制。在杆上，光适应性是由钙介导的，并且在光激活时钙减少的机制调节了光转导的钙均得到充分了解。虽然光激活还触发了锥体钙的下降，但尚不清楚这对锥体照射转导的负反馈的分子机制。此处描述的实验将采用可用遗传改性小鼠的生理研究，以研究钙通过钙调节锥光转导级联的调节机制。具体而言，我们将检验以下假设：视紫红质激酶通过恢复蛋白对视觉色素磷酸化的调节是小鼠锥体中钙反馈的组成部分，并在黑暗和光适应过程中调节其光转移。我们还将检验以下假设：鸟叶烯基环酶通过鸟叶烯基环酶激活蛋白（GCAP）对CGMP合成的调节是小鼠锥体中钙反馈的主要组成部分，并调节它们在黑暗和光适应过程中的光传输。这些实验将共同确定允许锥体适应非常广泛的光强度并全天保持功能的机制，即使是在明亮的光线下也保持起作用。 公共卫生相关性：该提案中概述的实验旨在建立使哺乳动物锥体在明亮的光下起作用的机制，这是介导白天视觉的光感受器的重要属性。这些研究将有助于我们了解钙在正常和病理条件下调节哺乳动物锥功能中的作用。