Calcium channels at ribbon synapses in the retina

视网膜带状突触的钙通道

• 批准号: 6722622
• 负责人: CATHERINE W MORGANS
• 金额: $ 26.43万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6722622
• 关键词: biophysics; calcium channel; cell biology; cone cell; congenital vision disorder; electrophysiology; genetic disorder; glutamates; immunocytochemistry; laboratory mouse; laboratory rat; neural information processing; neural transmission; night blindness; protein protein interaction; protein structure function; retina; rod cell; synapses; syntaxin; tissue /cell culture; visual stimulus

DESCRIPTION (provided by applicant): Recently the gene causing incomplete congenital stationary night blindness (CSNB2) was identified and found to encode a retina-specific, voltage-activated calcium channel, alpha-1F. The disease is characterized by severely reduced nighttime (or rod-mediated) vision as well as abnormalities in daytime (or cone-mediated) vision. The electrophysiological and psychophysical phenotype of CSNB2 can be explained by a defect in synaptic transmission within the retina. We have found that the alpha-1F calcium channel is localized to rod photoreceptor and rod bipolar cell synaptic terminals in the rat and mouse retinas consistent with the night-blindness associated with CSNB2. Voltage-activated calcium channels are essential to the first two stages of visual processing in the retina, which occur at photoreceptor and bipolar cell ribbon synapses. At the ribbon synapse, calcium channels couple the graded electrical responses of the photoreceptor or bipolar cell to calcium-dependent, graded release of the excitatory neurotransmitter, glutamate. Our data suggest that the symptoms of CSNB2 are caused by a block of glutamate release at photoreceptor and bipolar cell ribbon synapses. A detailed characterization of the alpha -1F calcium channel is essential to understanding both the complex phenotype of CSNB2 and normal synaptic transmission in the retina. Yet the biophysical properties of alpha-1F calcium channels are not known. Nor is it known whether alpha-1F is present in cone photoreceptor and cone bipolar cell terminals, or whether other calcium channels mediate glutamate release in the cone pathway. The proposed experiments will address these questions. The Specific Aims are to 1. Determine in detail the distribution and functional properties of the alpha-1F calcium channel subunit. 2. Identify retinal proteins that interact with alpha-1F. 3. Identify other voltage-activated calcium channels at retinal ribbon synapses. We will use a multidisciplinary approach involving molecular, biochemical, immunohistochemical and electrophysiological techniques to achieve these aims. The results of these experiments will provide insight into the composition and functional organization of retinal ribbon synapses and into the perturbation of retinal function associated with CSNB2.

描述（由申请人提供）：鉴定出导致不完全的先天性夜间失明（CSNB2）的基因，并发现该基因编码视网膜特异性的，电压激活的钙通道Alpha-1f。该疾病的特征是白天（或锥形介导的）视力严重降低了夜间（或杆介导的）视力以及异常。 CSNB2的电生理和心理物理表型可以通过视网膜内突触传播的缺陷来解释。我们已经发现，α-1F钙通道位于大鼠和小鼠视网膜中的杆光感受器和杆双极细胞突触端，与与CSNB2相关的夜盲性一致。 电压活化的钙通道对于视网膜中视觉处理的前两个阶段至关重要，视网膜发生在光感受器和双极细胞色带突触下。在色带突触，钙通道对光感受器或双极细胞的分级电响应对钙依赖性的，分级的兴奋性神经递质（谷氨酸）的分级释放。我们的数据表明，CSNB2的症状是由光感受器和双极细胞色带突触下的谷氨酸释放块引起的。 Alpha -1F钙通道的详细表征对于理解视网膜中CSNB2和正常突触传递的复杂表型至关重要。然而，尚不清楚α-1F钙通道的生物物理特性。也不知道锥形感受器和锥双极细胞末端中是否存在α-1F，或者其他钙通道是否介导锥途径中的谷氨酸释放。 拟议的实验将解决这些问题。具体目的为1。详细确定α-1F钙通道亚基的分布和功能特性。 2。确定与α-1F相互作用的视网膜蛋白。 3。在视网膜色带突触上确定其他电压激活的钙通道。我们将使用涉及分子，生化，免疫组织化学和电生理技术的多学科方法来实现这些目标。 这些实验的结果将洞悉视网膜色带突触的组成和功能组织，以及与CSNB2相关的视网膜功能的扰动。