VISUAL TRANSDUCTION IN RETINAL PHOTORECEPTORS

拟议研究的长期目标是了解 详细介绍视网膜视觉传导的细胞机制 杆状和锥状感光器。 第一个具体目标是更多地了解光适应和 杆状体内潜在的钙离子反馈。特别是，我们希望 检查：a)cGMP门控通道对钙离子选择性的任何变化 在背景光下，b)鸟苷环化酶( CGMP合成酶)和近生理条件下的Ca++， C)独立于背景光的任何剩余背景光适应 Ca++反馈和d)电压相关电导的任何贡献 对杆的电压响应所显示的光适应。 第二个具体目标是更多地了解 球果的光传导机制与光适应。在……里面 具体地说，我们希望找出：a)暗代谢流量是否 CGMP比杆状更快，b)是否调制了锥体 钙离子介导的鸟苷环化酶在数量上与杆状的相似 酶，以及c)在圆锥体上进行的各种测量是否可以 集成在一个简单的模型中，以预测圆锥体的响应行为 灯。 第三个特定的目的是表征视网膜cGMP激活的 分子水平上的通道。我们希望：a)使结构-功能 杆状通道基因定点突变的相关性研究 以及杆通道和杆通道之间嵌合通道的构造 嗅觉纤毛中的同源通道，以及b)分子克隆 CGMP门控通道在视锥细胞中，也可能在视网膜的其他地方。 电生理实验将在两栖动物身上进行 视杆和视锥以及哺乳动物视锥。分子生物学 研究将与平行的电学测量一起进行。 人视网膜cGMP激活通道的OUT研究 图书馆。 对光传导过程的详细了解对于 了解影响光感受器的各种疾病，如 视网膜色素变性。

The long-term objective of the proposed research is to understand in detail the cellular mechanisms underlying visual transduction in retinal rod and cone photoreceptors. The first specific aim is to understand more about light adaptation and the underlying Ca++ feedback in rods. In particular, we hope to examine: a) any change in the cGMP-gated channel's selectivity for Ca++ in background light, b) the relation between guanylate cyclase (the cGMP-synthesizing enzyme) and Ca++ under near-physiological conditions, c) any residual background light adaptation that is independent of the Ca++ feedback and d) any contribution of voltage-dependent conductances to the light adaptation shown by the voltage response of rods. The second specific aim is to understand more about the phototransduction mechanism and light adaptation in cones. In particular, we hope to find out: a) whether the dark metabolic flux for cGMP is faster than in rods, b) whether the modulation of the cone guanylate cyclase by Ca++ is quantitatively similar to that for the rod enzyme, and c) whether the various measurements made on cones can be integrated in a simple model to predict the cone's response behavior to light. The third specific aim is to characterize the retinal cGMP-activated channels at a molecular level. We hope to: a) make structure-function correlation studies of the rod channel through site-directed mutagenesis as well as construction of chimeric channels between the rod channel and a homologous channel in olfactory cilia, and b) molecularly clone the cGMP-gated channels in cones and possibly elsewhere in the retina. The electrophysiological experiments will be carried out on amphibian rods and cones as well as mammalian cones. The molecular biological studies, together with parallel electrical measurements, will be carried out on cGMP-activated channels derived from a human retinal cDNA library. A detailed knowledge of the phototransduction process is important for understanding various diseases affecting photoreceptors, such as retinitis pigmentosa.