High resolution study of presynaptic calcium influx

突触前钙流入的高分辨率研究

• 批准号: 7164451
• 负责人: STEPHEN D MERINEY
• 金额: $ 20.81万
• 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 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7164451
• 关键词: Action Potentials; Aftercare; Age; Agonist; Anatomy; Appearance; Attention; Calcium; Calcium Channel; Calcium ion; Characteristics; Chromosome Pairing; Data; Disruption; Distal; Dose; Drops; Event; Family; Figs - dietary; Frequencies; G-Protein-Coupled Receptors; GTP-Binding Proteins; Goals; Heterogeneity; Image; Individual; Knowledge; Laboratories; Length; Maps; Mediating; Methionine Enkephalin; N-Type Calcium Channels; Nature; Nerve; Neuromuscular Junction; Neurons; Norepinephrine; Numbers; Pattern; Pertussis Toxin; Physiology; Preparation; Principal Investigator; Probability; Process; Proteins; Rana; Reporting; Research; Resolution; Signal Transduction; Site; Spatial Distribution; Speed; Staining method; Stains; Stimulus; Structure; Substance P; Suramin; Synapses; Synaptic Transmission; Testing; Time; Vesicle; Work; base; chemical release; driving force; extracellular; fluorescence imaging; inhibitor/antagonist; interest; mastoparan; omega-Conotoxins; postsynaptic; presynaptic; receptor; release of sequestered calcium ion into cytoplasm; research study; size; voltage gated channel

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 determines 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.

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严格的调控 通过钙离子的流动进入突触前神经元的特殊活动区。这个 钙离子内流的大小、时间和空间分布决定了 释放了。我们建议在青蛙神经肌肉交界处使用高速成像来增加我们的 了解调节该突触释放的钙内流轮廓的空间分布。 青蛙神经肌肉接头是一种典型的突触准备，具有大而有组织的活性 区域。因此，该制备结合了有利于钙成像的空间组织 具有丰富的生理和生理背景信息的单个活动区的水平 对这种突触的解剖。我们建议用快速的时间分辨率来刻画空间 钙内流沿神经肌肉接头长度的分布。我们将检验这一假设 单个钙离子通道的开放会产生刺激诱发的钙离子内流部位，而单个 通道开放触发青蛙神经肌肉接头的递质释放。此外，我们正在 有兴趣研究G蛋白对电压门控通道钙内流的调节作用 在这个突触。这些研究将加深我们对递质释放及其调制的理解。

项目成果

Spatial Distribution of Calcium Entry Evoked by Single Action Potentials within the Presynaptic Active Zone.

突触前活动区内单一动作电位引起的钙进入的空间分布。

• DOI: 10.1523/jneurosci.1660-03.2004
• 发表时间: 2004
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Wachman,ElliotS;Poage,RobertE;Stiles,JoelR;Farkas,DanielL;Meriney,StephenD
• 通讯作者: Meriney,StephenD