Calcium channels in retinal photoreceptors

视网膜感光细胞中的钙通道

• 批准号: 10331169
• 负责人: AMY LEE
• 金额: $ 32.06万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2022-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10331169
• 关键词: 3-Dimensional; Affect; Aging; Binding; Biochemical; Biological; Blindness; Brain; Calcium Channel; Cell Transplantation; Cell surface; Cells; Characteristics; Communication; Cone; Defect; Dendrites; Development; Disease; Electron Microscopy; Electrophysiology (science); Electroporation; Functional disorder; Genetic; Glutamates; Goals; Heart; Image; Inherited; Injury; Knock-out; Knockout Mice; Knowledge; Mediating; Membrane; Metabotropic Glutamate Receptors; Microscopy; Modeling; Mus; Mutation; Night Blindness; Organelles; Outcomes Research; Photoreceptors; Presynaptic Terminals; Process; Property; Proteins; Proteomics; Research Priority; Resolution; Retina; Retinal Detachment; Retinal Diseases; Retinal Photoreceptors; Rod; Role; Signal Transduction; Structure; Synapses; Techniques; Testing; Vertebrate Photoreceptors; Vision Disorders; Visual; Work; cone-rod dystrophy; extracellular; in vivo; mutant; neurotransmission; neurotransmitter release; novel; novel strategies; novel therapeutics; optical imaging; postsynaptic; presynaptic; prevent; ribbon synapse; scaffold; sight restoration; synaptic function; synaptogenesis; transplantation therapy; voltage

Communication at the first visual synapse is mediated by L-type voltage-gated Cav1.4 Ca2+ channels. These channels are concentrated in the synaptic terminal beneath the ribbon, an organelle characteristic of synapses employing tonic neurotransmitter release. Mutation of Cav1.4 alters neurotransmission but can also prevent synaptic development. Such defects can present as a variety of visual diseases, including congenital stationary night blindness or cone-rod dystrophy. In this proposal, we will test the hypothesis that Cav1.4 (Aim 1) and its auxiliary subunits, β2 (Aim 2) and α2δ4 (Aim 3), are each essential in various ways for synaptic development in photoreceptors. This work will be accomplished using a complementary array of electrophysiological, genetic, biochemical, and cell biological approaches. The outcomes of this research should have a broad impact by transforming the concept of how Cav1.4 channels contribute to synapse function and disease-triggered remodeling.

第一个视觉突触的通信由L型电压门控CAV1.4 Ca2+介导 频道。这些通道集中在丝带下方的突触末端 使用滋补神经递质释放的突触的细胞器特征。突变 CAV1.4改变神经传递，但也可以防止突触发育。这样的缺陷可以 作为各种视觉疾病，包括先天性静止的夜失明或锥体杆营养不良。在此提案中，我们将测试Cav1.4（AIM 1）及其辅助的假设 亚基β2（AIM 2）和α2Δ4（AIM 3）在各种方面都必须进行突触 光感受器的发展。这项工作将使用完整的数组完成 电生理，遗传，生化和细胞生物学方法。结果的结果 研究应该通过改变CAV1.4渠道的概念来产生广泛的影响 有助于突触功能和疾病触发的重塑。