High resolution study of presynaptic calcium influx

突触前钙流入的高分辨率研究

• 批准号: 6574906
• 负责人: STEPHEN D MERINEY
• 金额: $ 33.84万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6574906
• 关键词: G protein; Rana; action potentials; biological signal transduction; calcium channel; calcium channel blockers; calcium flux; image processing; neural transmission; neuromuscular junction; neurotransmitter transport; receptor coupling; synapses; voltage gated channel

DESCRIPTION (provided by applicant): Neurons communicate using electrical activity, but the exchange of information between neurons usually requires the release of chemical messengers. This fast synaptic transmission is tightly regulated by the flux of calcium ions into specialized active zone regions of the presynaptic neuron. The magnitude, timing, and spatial distribution of calcium influx determine the amount of transmitter that is released. We propose to use high speed imaging at the frog neuromuscular junction to increase our understanding of the spatial distribution of the calcium influx profiles that regulate release at this synapse. The frog neuromuscular junction is a classic synaptic preparation with large and well-organized active zones. As such, this preparation combines a spatial organization that is favorable for calcium imaging at the level of single active zones with a wealth of background information related to the physiology and anatomy of this synapse. We propose to characterize with fast temporal resolution the spatial distribution of calcium influx along the length of the neuromuscular junction. We will test the hypothesis that the opening of a single Ca2+ channel generates a stimulus-evoked Ca2+ entry site and that single channel openings trigger transmitter release in the frog neuromuscular junction. In addition, we are interested in studying the effects of G protein modulation of calcium influx through voltage-gated channels at this synapse. These studies will increase our understanding of transmitter release and its modulation.

描述（由申请人提供）：神经元通过电活动进行交流，但神经元之间的信息交换通常需要释放化学信使。这种快速的突触传递受到钙离子进入突触前神经元的特殊活动区的通量的严格调节。钙内流的幅度、时间和空间分布决定了释放的递质量。我们建议在青蛙神经肌肉连接处使用高速成像，以增加我们对调节该突触释放的钙流入剖面的空间分布的理解。青蛙的神经肌肉连接是一个典型的突触准备，具有大而组织良好的活动区。因此，这种制备结合了有利于钙成像的空间组织和丰富的与该突触生理学和解剖学相关的背景信息。我们建议表征与快速时间分辨率的空间分布钙流入沿神经肌肉交界处的长度。我们将测试单一Ca2+通道的打开产生刺激诱发的Ca2+进入位点的假设，并且单一通道打开触发青蛙神经肌肉连接处的递质释放。此外，我们有兴趣研究G蛋白通过该突触的电压门控通道调节钙内流的作用。这些研究将增加我们对发射机释放及其调制的理解。