TRP CHANNEL EXPRESSION AND FUNCTION IN ON-BIPOLAR CELLS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 在视网膜中，视觉信息被分成不同的路径，这些路径对光强度的增加和减少做出反应。在第一次视网膜突触，谷氨酸从光感受器终端的紧张性释放在黑暗中保持较高的突触浓度，对光的反应减少。两种类型的突触后细胞，即开双极细胞和离双极细胞，对光感受器释放的谷氨酸做出相反的极性反应。ON-双极细胞信号通路起源于一种独特的代谢性谷氨酸受体mGluR6，它存在于ON-双极细胞的树突上。MGluR6通过G蛋白GO调节一种未知阳离子通道的活性，从而光诱导突触谷氨酸的减少打开该通道并使细胞去极化。 先天性静止性夜盲(CSNB)是一组以暗视为特征的非进行性视网膜疾病。许多基因的突变已被证明与CSNB有关。一个这样的例子是编码mGluR6的基因GRM6的突变。最近，有报道称，Appaloosa马的CSNB与导致TRPM1阳离子通道表达减少的突变有关。我们假设TRPM1和其他相关的Trp通道是与mGluR6偶联的阳离子通道。结合生化、免疫组织化学和电生理学方法，我们发现TRPM1是双极细胞去极化光反应所必需的，而且TRPM1是产生这种光反应的阳离子通道的一个组成部分。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In the retina, visual information is segregated into pathways that respond to increases and decreases in light intensity. At the first retinal synapse, the tonic release of glutamate from photoreceptor terminals maintains a high synaptic concentration in darkness that decreases in response to light. Two types of postsynaptic cells, the ON- and OFF-bipolar cells, respond with opposite polarity to glutamate released by photoreceptors. The ON-bipolar cell signaling pathway originates with a unique metabotropic glutamate receptor, mGluR6, which is found on the dendrites of ON-bipolar cells. mGluR6 acts via a G-protein, GO, to regulate the activity of an unidentified cation channel such that the light-induced decrease in synaptic glutamate opens the channel and depolarizes the cell. Congenital stationary night blindness (CSNB) is a group of non-progressive retinal diseases characterized by impaired scotopic vision. Mutations in a number of genes have been shown to be associated with CSNB. One such example are mutations in GRM6, the gene encoding mGluR6. Recently, it has been reported that CSNB in Appaloosa horses is associated with a mutation causing a reduced expression of the TRPM1 cation channel. We hypothesized that TRPM1, and possibly other related TRP channels, are the cation channels coupled to mGluR6. Using a combination of biochemical, immunohistochemical, and electrophysiological approaches, we have found that TRPM1 is necessary for the depolarizing light response of ON-bipolar cells, and further that TRPM1 is a component of the cation channel that generates this light response.