PHYSIOLOGY OF PHOTORECEPTORS

描述(改编自申请者的摘要)：钙在 在光感受器转导中扮演第二信使的角色。信号的调制 如果钙离子在光和暗适应期间不发生敏感性 防止外段改变，以及钙离子的变化 浓度被认为在钙离子依赖的速度上产生变化。 鸟苷酸环化酶、视紫红质增益和寿命，以及cGMP门控通道开放。 Ca~(2+)在视网膜光感受器死亡中也可能起中心作用 退化。因为对游离钙离子浓度的调节至关重要 对光感受器的正常生理很重要，也可能 在退行性变的病因学中很重要，游离钙的测定是 对于我们理解这一重要感官的细胞生物学至关重要 受体。因此，研究人员开发了一种新的技术，称为 斑点共聚焦显微镜，以测定黑暗中的钙水平和 定量测定细胞内游离钙离子浓度的变化 由刺激产生的。这项技术更加灵活，而且 比以前的方法更灵敏，已经被用来进行精确的测量 钙离子不仅存在于两栖动物的视杆和视锥中，而且还存在于两栖动物的光感受器中 哺乳动物，如老鼠。在此应用程序中，调查员建议使用 电生理学和斑点共聚焦显微镜回答两个问题 对光感受器的生死至关重要。第一，要 阐述光照如何改变两栖动物体内的游离钙离子浓度 光感受器，将使用各种技术来研究 火蜥蜴杆状和球果的光依赖性钙离子释放和再吸收。 其次，为了解决光如何改变其他生物中的游离钙离子的问题， 特别是哺乳动物，转基因动物的测量结果将被用于 探讨光依赖性钙释放和再摄取的机制，并 探讨钙离子浓度与钙离子浓度之间的可能相关性。 启动细胞凋亡和细胞死亡。

DESCRIPTION (Adapted from the applicant's abstract): Calcium plays a central role as a second messenger in photoreceptor transduction. The modulation of sensitivity during light and dark adaptation does not occur if Ca2+ is prevented from changing in the outer segment, and the change in Ca2+ concentration is thought to produce Ca2+-dependent changes in the rate of guanylyl cyclase, rhodopsin gain and lifetime, and cGMP-gated channel opening. Ca2+ may also play a central role in photoreceptor death during retinal degeneration. Since the regulation of the free Ca2+ concentration is vitally important to the normal physiology of the photoreceptor and may also be important in the etiology of degeneration, the measurement of free Ca2+ is crucial for our understanding of the cell biology of this important sensory receptor. The investigator has, therefore, developed a novel technique, called spot confocal microscopy, to determine the level of Ca2+ in darkness and to make quantitative measurements of the changes in free Ca2+ concentration produced by stimulation. This technique is considerably more flexible and sensitive than previous methods and has been used to make accurate measurements of Ca2+ not only in amphibian rods and cones but also in the photoreceptors of mammals such as mice. In this application, the investigator is proposing to use electrophysiology and spot-confocal microscopy to answer two questions of fundamental importance to the life and death of photoreceptors. First, to address how light changes the free Ca2+ concentration in amphibian photoreceptors, a variety of techniques will be used to investigate light-dependent Ca2+ release and re-uptake from salamander rods and cones. Second, to address how light changes the free Ca2+ in other organisms, particularly mammals, measurements from transgenic animals will be used to probe the mechanism of light-dependent Ca2+ release and re-uptake, and to explore a possible correlation between the Ca2+ concentration and the initiation of apoptosis and cell death.