CALCIUM FEEDBACK MECHANISMS IN VISUAL ADAPTATION

描述(改编自申请人的摘要)：调查 调节视觉适应的分子事件，将使用小鼠遗传学 靶向光传导的特定成分。电生理学 对这些基因工程小鼠的光感受器的测量将 用于研究特定成分在体内条件下的作用和 在实时动力学下。生化分析将与 这些测量描绘了生理机制背后的分子机制 表型。使用这种多学科方法，调查员提出： (1)有针对性地系统消除已知的钙反馈环 破坏被认为是调节反馈的钙结合蛋白； (2)消除钙-钙调蛋白对环状GMP的调节 (CGMP)门控通道，使用在 CGMP门控通道的β亚基，破坏整体适应 过程，并评估钙离子反馈在调节视觉适应中的作用。 进一步的研究将探讨鸟苷的恢复机制。 杆状细胞中的环化酶(GC)和鸟苷环化酶激活蛋白(GCAPs) 感光反应。最后，cGMP升高与cGMP的关系 将对光感受器细胞死亡进行调查。

Description (Adapted from the applicant's abstract): To investigate the molecular events that regulate visual adaptation, mouse genetics will be used to target specific components of phototransduction. Electrophysiological measurements of the photoreceptors from these genetically-engineered mice will be used to study the role of particular components under in vivo conditions and under real-time kinetics. Biochemical assays will be used in conjunction with these measurements to delineate the molecular mechanisms behind the physiologic phenotypes. Using this multi-disciplinary approach, the investigator proposes: (1) to systematically remove the known Ca2+-feedback loops by targeted disruption of Ca2+ binding proteins that are thought to mediate the feedback; and (2) to eliminate regulation by Ca2+-calmodulin on the cyclic GMP (cGMP)-gated channel, using mice harboring a target mutation on the beta-subunit of the cGMP-gated channel that disrupts the overall adaptation process, and assess the role of Ca2+-feedback in regulating visual adaptation. Further studies will investigate the recovery mechanisms involving guanylate cyclases (GCs) and guanylate cyclase activating proteins (GCAPs) in rod photoreceptor response. Finally, the relationship between elevated cGMP and photoreceptor cell-death will be investigated.