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

基本信息

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
项目类别：
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

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

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项目摘要

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.

该提案的目的是检查内部Ca2 +商店在在该神经植物神经末端后垂体。这些末端隔离催产素或精氨酸加压素，其具有有据可查的生理行动对水平衡，血压，分娩和也许甚至心情。另外，可以隔离任何关联的单个终端结构，用于调节外施加病的电生理和光学研究在细胞器和分子水平。因此，本提案与两者都相关临床应用和基本科学理解。在胞吐作用的经典模型中 +通过电压激活的Ca2 +通道从外部进入神经末端细胞质和触发胞吐作用。但是，正如我们在神经型末端所证明的那样，Ca2 + 也可以从内膜膜结合的Ca2 +储存中进入胞质溶胶。版本从商店开始，以Ca2 + Syntillas的形式进行数量，类似于Ca2 +火花肌肉。（scintilla，拉丁语火花，由神经终端引起，通常是突触结构。）Ca2 + Santillas是由于Ca2 +通过一种内部物种进入细胞质的原因 Ca2 +通道称为Ryanodine受体（RYR），它们可能自发发生或为引起。它们不会引发胞吐作用。主要目的是建立CA2 +的效果自发性和引起的胞吐作用上的征含量和Ca2 +存储。我们知道义曲不引起胞吐作用，我们的初步数据表明义曲实际上抑制了胞吞作用。我们希望确定这一点，并确定含义是如何做到这一点的。有两种一般的可能性 - 义曲抑制完整的融合事件，仅允许突触囊泡的部分排空。否则征纹可以抑制人口的释放较大的囊泡 - 或两者兼而有之。