Light Adaptation in Vertebrate Rod Photoreceptors

脊椎动物杆状感光器的光适应

• 批准号: 6518667
• 负责人: CLINT L MAKINO
• 金额: $ 25.9万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6518667
• 关键词: Urodela; calcium ion; cyclic GMP; electrodes; electrophysiology; genetically modified animals; laboratory mouse; light adaptations; light intensity; phosphodiesterases; phosphorylation; protein binding; protein kinase A; rod cell; transducin; visual photoreceptor; visual photosensitivity; visual phototransduction; voltage /patch clamp

DESCRIPTION (provided by applicant): Rod photoreceptors approach the ultimate in sensitivity to light but are also capable of adjusting that sensitivity over a wide range of ambient lighting conditions. This process of light adaptation is important because it extends the dynamic range over which rods are capable of encoding visual information. The goal of these studies is to understand the molecular bases for the changes in rod photoreceptor sensitivity that take place in the presence of steady illumination. Light adaptation is known to involve Ca+2 feedback onto the phototransduction cascade accelerating rhodopsin shutoff, increasing cGMP production and opening ion channels at lower levels of cGMP. At least some of these feedback mechanisms operate rapidly and cause the response to steps of light to partially recover or droop. This droop is essentially complete in a few seconds and helps to keep the rod from saturating so that it can continue to signal changes in light intensity. From suction electrode recordings on single rods of amphibians, we have obtained evidence that there is a component of light adaptation that operates on a slower time scale. The time course and magnitude of desensitization of the slow component will be measured. The dependency of the slow component upon Ca+2 feedback will be determined. Then three putative mechanisms will be tested: transducin's lifetime shortens as cGMP dissociates from noncatalytic sites on PDE, transducin availability decreases because phosducin prevents its recycling, the cGMP-gated channel opens at lower concentrations of cGMP due to a change in its apparent affinity for cGMP. The three mechanisms are not mutually exclusive. Interestingly, light adaptation in amphibian rods far surpasses that in mammalian rods. Two hypotheses will be explored. First, biochemical methods will be used to test whether the decrease in transducin's lifetime during light adaptation in amphibian rods due to the dissociation of cGMP from noncatalytic sites on phosphodiesterase fails to occur in mammalian rods, because cGMP binds much more tightly to these sites on mammalian PDE. Second, rare, aberrant, prolonged single photon responses occur in mammalian rods, but have not been seen in amphibian rods. The cumulative effects of aberrant responses during exposures to steps of light may drive mammalian rods into saturation prematurely. Suction electrode recording will be used to assess the impact of aberrant responses on light adaptation in wild type mouse rods and in rods where the frequency of aberrant responses is higher than normal. Aberrant responses occur with higher frequency in some human retinal diseases and severely limit the intensity range of scotopic vision.

描述（由申请人提供）：杆光感受器接近终极 对光的敏感性，但也能够调整这种灵敏度 各种环境照明条件。光适应过程 很重要，因为它扩展了杆的动态范围 编码视觉信息。这些研究的目的是了解 分子碱基，用于杆感光受体灵敏度的变化 放置在稳定照明的情况下。已知光适应 涉及CA+2反馈到光转导的级联ACGELATING RHOPOPSIN 关闭，增加了CGMP的生产和开放离子通道的较低水平 CGMP。这些反馈机制中至少有一些迅速运行，并导致 对光步骤的响应部分恢复或下垂。这个下垂是 本质上几秒钟内完成，并有助于防止杆饱和 这样它就可以继续发出光强度变化。来自吸力 在两栖动物的单杆上的电极记录，我们获得了证据 有一个光适应的组成部分可以在较慢的时间内运行 规模。慢组分的时间过程和脱敏的大小 将测量。慢组分对Ca+2反馈的依赖性将 可以确定。然后将测试三种推定的机制：跨杜以兑换 随着CGMP从PDE上的非催化位点解离，终身缩短， 跨蛋白的可用性会降低，因为磷素阻止了其回收利用， CGMP门控通道由于其变化而以较低浓度的CGMP打开 CGMP的明显亲和力。这三种机制不是相互排斥的。 有趣的是，两栖杆的光适应远远超过 哺乳动物棒。将探讨两个假设。首先，生化方法 将用于测试光线降低在光中的寿命 由于CGMP与非催化的解离，两栖动物棒的适应 磷酸二酯酶的位点在哺乳动物棒中未能发生，因为CGMP结合 在哺乳动物PDE上的这些站点更加紧密。第二，罕见，异常， 长时间的单光子反应发生在哺乳动物棒中，但没有 在两栖杆中可见。异常反应的累积影响 暴露于光线的台阶可能会使哺乳动物棒饱和 过早。吸气电极记录将用于评估 野生型小鼠杆和杆中的光适应性反应异常 异常响应的频率高于正常情况。异常 在某些人类视网膜疾病中，反应以较高的频率发生，并且 严重限制了Scotopic Vision的强度范围。