Regulation and Function of Internal Ca2+ Stores in Nerve Terminals

本建议的目的是研究内部钙库在 下丘脑大细胞神经元的神经垂体神经末梢 垂体后叶这些末端分泌催产素或精氨酸加压素， 对水平衡、血压、分娩和 甚至是情绪此外，单个端子可以在没有任何相关 结构和用于调节外生的电生理和光学研究 在细胞器和分子水平上。因此，本建议对双方都有意义。 临床应用和基本的科学理解。在胞吐作用的经典模型中，Ca 2 + 通过电压激活的Ca 2+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终末所证明的， 也可以从终末内膜结合的Ca 2+库进入胞质溶胶。释放 来自商店的是量子的，采取Ca 2 + syntillas的形式，类似于在 肌肉.（Scintilla，拉丁语为火花，来自神经末梢，通常是突触 结构。）Ca 2+合胞体的产生是由于Ca 2+通过一种内部通道进入细胞质。 钙通道称为Ryanodine受体（RyR），它们可以自发发生或 引出的它们不触发胞吐作用。主要目的是确定Ca 2+的作用 突触体和Ca 2+储存对自发和诱发的胞吐作用的影响。我们知道 合成体不引起胞吐作用，我们的初步数据表明合成体实际上抑制 胞吐作用我们希望确定这一点，并确定syntillas如何做到这一点。 一般有两种可能性-合成体抑制完全融合事件， 突触囊泡的部分排空。或者合成体可能会抑制种群的释放 或者两者都有

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.