CIRCADIAN REGULATION OF CGMP-GATED ION CHANNELS

CGMP 门控离子通道的昼夜节律调节

• 批准号: 6555833
• 负责人: GLADYS Y KO
• 金额: $ 5.21万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-28 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6555833
• 关键词: biological signal transduction; chickens; circadian rhythms; cyclic AMP; cyclic GMP; dopamine; dopamine antagonists; dopamine receptor; enzyme activity; immunocytochemistry; membrane channels; mitogen activated protein kinase; neurobiology; phosphatase inhibitor; protein tyrosine phosphatase; visual photoreceptor; visual phototransduction; voltage gated channel; western blottings

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.

描述（摘自申请人的摘要）： 昼夜节律振荡器在门控性能中引起翻译后调节 CGMP门控通道的鸡视网膜中的CGMP的亲和力为 在主观的夜晚更高。 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 这些渠道的门控行为。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。褪黑激素是合成的， 由光感受器分泌，而dA被合成和分泌 聚作者和/或链膜间细胞的亚群。褪黑激素和DA水平 在昼夜节律期间处于反相。褪黑激素不会产生任何 对光感受器的影响，但DA引起了对 感光体，包括通过D2诱导轻型相移的感受器 受体。这项研究将进一步研究基础的细胞机制 CGMP门控通道的昼夜节律调节和相关调节 DA通过以下特定目的进行CGMP门控通道：（1）了解 ERK和CAMKII的信号转导途径如何导致时钟控制 CGMP门控通道的通道门控性能，以及（2）确定机制 DA对CGMP门控通道的相位依赖性调制的调制。