CIRCADIAN REGULATION OF CGMP-GATED ION CHANNELS

描述(摘自申请人的摘要)： 昼夜节律振荡器在门控特性中引起翻译后调制 鸡视网膜视锥细胞中cGMP门控通道，其中与cGMP的亲和力是 在主观的夜晚更高。ERK和CaMKII都是输出的一部分 光感受器中的核心昼夜节律振荡器连接到 这些通道的选通行为。视网膜的昼夜节律也是 部分由多巴胺(DA)和褪黑素介导。褪黑激素被合成并 由光感受器分泌，而DA由 无长突细胞和/或网状细胞亚群。褪黑素和多巴胺水平 在昼夜节律周期中处于反相。褪黑素不会产生任何 对光感受器的影响，但DA在 光感受器包括通过D2诱导类光相移 感受器。这项研究将进一步研究潜在的细胞机制 CGMP门控通道的昼夜节律和相依调制 DA对cGMP门控通道的研究有以下具体目的：(1)了解 ERK和CaMKII信号转导通路是如何导致细胞周期调控的 CGMP门控通道的门控特性，以及(2)识别机制 DA对cGMP门控通道的相依调制。

DESCRIPTION (from the Applicant's Abstract): Circadian oscillators cause a posttranslational modulation in gating properties of cGMP-gated channels in chick retina cones, in which the affinity for cGMP is higher during the subjective night. Both Erk and CaMKII are part of the output pathway coupling the core circadian oscillator in the photoreceptors to the gating behavior of these channels. Circadian rhythms in retina are also mediated in part by dopamine (DA) and melatonin. Melatonin is synthesized and secreted by photoreceptors, while DA is synthesized and secreted by subpopulations of amacrine and/or interplexiform cells. Melatonin and DA levels are in antiphase during the circadian cycle. Melatonin does not produce any effect on photoreceptors, but DA evokes several direct effects on photoreceptors including the induction of light-like phase-shifts via D2 receptors. This research will further study the cellular mechanism underlying circadian regulation of cGMP-gated channels and the phase-dependent modulation of cGMP-gated channels by DA in the following specific aim: (1) to understand how the signal transduction pathways of Erk and CaMKII lead to clock control of channel gating properties of cGMP-gated channels, and (2) to identify mechanism of phase-dependent modulation of cGMP-gated channels by DA.