CIRCADIAN REGULATION OF CGMP-GATED ION CHANNELS

描述（来自申请人的摘要）： 昼夜节律振荡器引起门控特性的翻译后调制 鸡视网膜视锥细胞中cGMP门控通道，其中cGMP的亲和力是 在主观的夜晚。Erk和CaMKII都是输出的一部分 将光感受器中的核心昼夜节律振荡器耦合到 这些通道的门控行为。视网膜中的昼夜节律也是 部分由多巴胺（DA）和褪黑激素介导。褪黑素是合成的， 由光感受器分泌，而DA由 无长突细胞和/或网间细胞的亚群。褪黑素和DA水平 在生理周期中处于反相位。褪黑激素不产生任何 对光感受器的影响，但DA引起几种直接影响， 包括通过D2诱导类光相移的光感受器 受体。本研究将进一步探讨其细胞机制 cGMP门控通道的昼夜节律调节和相位依赖性调节 通过DA对cGMP门控通道的研究，其具体目的如下：（1）了解 Erk和CaMKII的信号转导途径如何导致生物钟控制 cGMP门控通道的通道门控特性，以及（2）识别机制 DA对cGMP门控通道的相位依赖性调节。

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.