STUDIES ON THE MECHANISM OF VISUAL EXCITATION

这项研究的长期目标是了解视觉的过程， 分子水平上的激发。 我们计划探索所有三个阶段， 视觉兴奋过程：初始转导事件，其中 被视觉色素吸收的光开始激发过程; 光活化视紫红质启动生物化学反应的机制 光感受器细胞内的事件;以及光感受器的控制 质膜透性 我们不仅将研究脊椎动物的杆，而且 我也将开发使用单克隆抗体的方法， 大量的视锥细胞和无脊椎光感受器及其 相关的视觉色素。 虽然对生物化学或 在生物病理学上，无论是色素，前者的缺陷是负责 治疗色盲 我们计划研究这两个地区的结构变化， 发色团和载脂蛋白时，视紫红质转化为其 特别是寻找光能的证据 通过电荷分离转化为化学能。 我们将 调查可能结合的性质和结构基础， 二价阳离子的视紫红质，并为光引发的相互作用 视紫红质与参与视杆中cGMP代谢的酶。 有 越来越多的证据表明，视网膜色素变性的某些方面可能是由于 光激活酶系统的缺陷。 调查这些 我们将使用各种各样的技术，包括蛋白质和 发色团改性;和圆二色性，低温， 荧光和振动光谱。 最后，我们将研究 通过尝试分离和纯化来控制杆膜中的离子通道 质膜和离子通道都使用单克隆抗体。

The long term goal of this research is to understand the process of visual excitation at the molecular level. We plan to explore all three stages of the visual excitation process: the intitial transduction event, where light absorbed by the visual pigment starts the excitation process; the mechanism by which the photo-activated rhodopsin initiates the biochemical events within the photoreceptor cell; and the control of photoreceptor plasma membrane permeability. We will study not only vertebrate rods, but also will develop methods using monocolonal antibodies to easily purify large quantities of cone and invertebrate photoreceptors and their associated visual pigments. While little is known biochemically or biophysically about either pigment, defects in the former are responsible for color blindness. We plan to study the structural changes in both the chromophore and the apoprotein when rhodopsin is transformed into its primary photoproduct and in particular look for evidence of light energy being transformed to chemical energy by charge separation. We will investigate both the nature and structural basis for probable binding of divalent cations by rhodopsin, and for the light initiated interaction of rhodopsin with enzymes involved in cGMP metabolism in the rods. There is growing evidence that certain aspects of retinitis pigmentosa may be due to defects in the light activated enzyme system. To investigate these interactions we will use a wide variety of techniques including protein and chromophore modification; and circular dichroic, low temperature, fluorescence, and vibrational spectroscopy. Finally we will study the control of ion channels in rod membranes by trying to isolate and purify both the plasma membrane and the ion channels using monoclonal antibodies.