PRESYNAPTIC MECHANISMS IN HAIR CELLS

毛细胞的突触前机制

• 批准号: 2377557
• 负责人: BRIAN WILLIAM EDMONDS
• 金额: $ 3.38万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-03-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2377557
• 关键词: Rana; calbindin; calcium; cellular polarity; diffusion; ear hair cell; exocytosis; membrane fusion; neural transmission; potassium channel; synapses; synaptic vesicles; synaptotagmin; tissue /cell culture; voltage /patch clamp

The long-term objective of this study is to understand mechanisms underlying Ca2+-mediated exocytosis during fast synaptic transmission. Chemical synapses are common sites for the manifestation of plastic changes thought to underlie some forms of learning, memory and developmental changes in the central nervous system. Moreover, synapses are also the targets of many neuroactive agents such as toxins and therapeutic drugs, and can become dysfunctional in certain types of neuropathology. A better understanding of synaptic function is therefore likely to be vital for advances in medical science. The mechanisms underlying exocytosis will be investigated in hair cells from the frog sacculus. These cells are ideally suited for the study of synaptic mechanisms, particularly the roles of Ca2+ and Ca2+-binding proteins (calbindin-D28k and synaptotagmin) in exocytosis. The specific aims are: (1) To test the hypothesis that the mobile Ca2+ buffer calbindin-D28k influences short-range Ca2+ signaling in frog saccular hair cells. (2) To test the hypothesis that increases in membrane capacitance induced by depolarization are due to the fusion of synaptic vesicles with the plasma membrane at active zones. This work will provide quantitative information about Ca2+ signaling and the release of neurotransmitter that should be applicable to other synapses in the nervous system.

本研究的长期目标是了解 在快速突触传递过程中潜在的Ca 2+介导的胞吐作用。 化学突触是可塑性神经元 改变被认为是某些形式的学习、记忆和 中枢神经系统的发育变化。此外，突触 也是许多神经活性剂如毒素和 治疗药物，并可能成为功能失调，在某些类型的 神经病理学因此，更好地了解突触功能 可能对医学的发展至关重要 的机制 将在青蛙的毛细胞中研究潜在的胞吐作用 球囊这些细胞非常适合研究突触 机制，特别是Ca 2+和Ca 2+结合蛋白的作用 （钙结合蛋白-D28 k和突触结合蛋白）。具体目标是： (1)为了验证假设，移动的Ca 2+缓冲calbindin-D28 k 影响青蛙囊状毛细胞中的短程Ca 2+信号。（二） 为了验证由细胞膜电容增加引起的假设， 去极化是由于突触囊泡与血浆的融合 活性区的膜。这项工作将提供定量信息 关于Ca 2+信号和神经递质的释放， 适用于神经系统中的其他突触。