Regulation and Function of Internal Ca2+ Stores in Nerve Terminals

神经末梢内部 Ca2 储存的调节和功能

• 批准号: 7932048
• 负责人: JOHN V WALSH
• 金额: $ 30.79万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-14 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7932048
• 关键词: Address; Adrenal Glands; Area; Argipressin; Atlases; Attention; Basic Science; Binding; Biological Models; Birth; Blood Pressure; Brain; Calcium; Cell membrane; Cells; Cerebellum; Chromaffin Cells; Clinical; Cognition; Coupling; Cytosol; Data; Dihydropyridine Receptors; Disease; Electric Capacitance; Electron Microscopy; Emotions; Encapsulated; Endoplasmic Reticulum; Equilibrium; Event; Exocytosis; Extracellular Space; Fluorescence Microscopy; Frequencies; Hand; Hippocampus (Brain); Hypothalamic structure; Image; Individual; Investigation; Knock-out; Label; Learning; Light; Measurement; Measures; Membrane; Memory; Methodology; Modeling; Molecular; Monitor; Moods; Muscle; Mutant Strains Mice; Nature; Nerve; Nerve Endings; Neurologic; Neurons; Neurotransmitters; Noise; Norepinephrine; Optics; Oxytocin; Paper; Physiological; Physiology; Population; Posterior Pituitary Gland; Presynaptic Terminals; Process; Proteins; Regulation; Research; Role; Running; RyR1; Ryanodine; Ryanodine Receptor Calcium Release Channel; Ryanodine Receptors; Serotonin; Shapes; Skeletal Muscle; Source; Speed; Spinal cord injury; Structure; Synapses; Synaptic Vesicles; Techniques; Testing; Thapsigargin; Vasopressins; Vesicle; Water; Work; base; clinical application; extracellular; interest; magnocellular; presynaptic; public health relevance; sensor; voltage

The purpose of this proposal is to examine the role of internal Ca2 + stores in neurohypophyseal nerve terminals of magnocellular hypothalamic neurons found in the posterior pituitary. These terminalssecrete Oxytocin or Arginine Vasopressin, which have well documented physiological actions on waterbalance, blood pressure, parturition and perhaps even mood. In addition single terminals can be isolatedwithout any associated structures and used for electrophysiological and optical studies of regulated exoctyosis at the organelle and molecular level. Thus, the present proposal has relevance for both clinical application and basic scientific understanding. In the classic model of exocytosis, Ca2 + enters the nerve terminal cytosol from the exterior through voltage-activated Ca2 + channels and triggers exocytosis. But, as we have demonstrated in neurohypophyseal terminals, Ca2 + may also enter the cytosol from intraterminal membrane bound Ca2 + stores. The release from stores is quantal, taking the form of Ca2 + syntillas, similar to Ca2 + sparks found in muscle. (Scintilla, Latin for spark, arising from a nerve terminal, normally a synaptic structure.) Ca2 + syntillas arise due to Ca2 + entering the cytosol through a species of internal Ca2 + channel called a ryanodine receptor (RyR), and they may occur spontaneously or be elicited. They do not trigger exocytosis. The major aim is to establish the effect of Ca2 + syntillas and Ca2 + stores on both spontaneous and elicited exocytosis. We know that syntillas do not elicit exocytosis, and our prelimary data indicates that syntillas actually inhibit exocytosis. We wish to establish this with certainty and to determine how syntillas do this. There are two general possibilities - that syntillas suppress full fusion events, allowing only partial emptying of a synaptic vesicle. Or the syntillas may suppress release of a population of larger vesicles - or both.

本提案的目的是研究内部 Ca2+ 储存在 下丘脑大细胞神经元的神经垂体神经末梢发现于 垂体后叶。这些终端分泌催产素或精氨酸加压素，它们具有 对水平衡、血压、分娩和 也许甚至是心情。此外，单个端子可以隔离，无需任何关联的 结构并用于调节性分泌的电生理学和光学研究 在细胞器和分子水平上。因此，本提案对于以下两个方面都具有相关性： 临床应用和基本科学理解。在经典的胞吐作用模型中，Ca2+ + 通过电压激活的 Ca2+ 通道从外部进入神经末梢细胞质 并触发胞吐作用。但是，正如我们在神经垂体末梢中所证明的那样，Ca2+ 也可能从末端膜结合的 Ca2+ 库进入细胞质。发布 商店中的 Quantal，采用 Ca2 + syntillas 的形式，类似于 Ca2 + 火花 肌肉。 （Scintilla，拉丁语，火花的意思，由神经末梢产生，通常是突触 结构。）Ca2+ Syntillas 是由于 Ca2+ 通过一种内部结构进入细胞质而产生的。 Ca2+ 通道称为兰尼碱受体 (RyR)，它们可能自发发生或被 引发。它们不会引发胞吐作用。主要目的是确定 Ca2+ 的作用 syntillas 和 Ca2+ 储存在自发的和诱发的胞吐作用中。我们知道 syntillas 不会引起胞吐作用，我们的初步数据表明 syntillas 实际上抑制 胞吐作用。我们希望确定这一点，并确定 Syntillas 如何做到这一点。 有两种一般的可能性 - Syntillas 抑制完全融合事件，只允许 突触小泡的部分排空。或者 Syntillas 可能会抑制种群的释放 较大的囊泡 - 或两者兼而有之。