DEPOLARIZATION SECRETION COUPLING IN NERVE TERMINALS

神经递质的释放是轴突棘波侵入神经的结果。 终点站。尽管有相当多的证据表明， 神经元胞体导致钙离子进入和随后的分泌。 神经递质和/或神经激素的分子细节 离子电流控制神经活性物质的释放 终端仍未确定。这项提议利用了 在哺乳动物系统中，这些问题可以被直接解决。大有可为 已经知道了大鼠神经垂体的电活动 随后它的多肽荷尔蒙释放得很好 特色化的。现在唯一可能制备的是分离的神经 这种神经内分泌结构的终末对 钙依赖释放识别的多肽引起的去极化 胞吐。最近的研究表明，从 神经垂体受特定的电活动模式的调节。 因此，这些神经末梢具有分析所需的所有性质 详细介绍了去极化-分泌耦合的过程。我们建议 应用膜片钳和生化方法研究电生理学 从分泌的多肽来看，神经末梢与 神经荷尔蒙的不同释放。我们特别建议 为了详细描述在这些神经末梢发现的钙通道 并确定哪些对后叶加压素的释放是重要的 催产素。此外，我们将寻找可能的终端内站点 钙离子作用导致这些神经活性物质的胞吐分泌 物质。阐明这种现象背后的分子机制 相互作用将代表着理解如何 神经元之间的通讯是有规律的。

Neurotransmitter release occurs as a result of axonal spikes invading nerve terminals. Although there is considerable evidence that depolarization of neuronal somata leads to the entry of Ca2+ and to the subsequent secretion of neurotransmitters and/or neurohormones, the molecular details of how ionic currents control the release of neuroactive substances from nerve terminals remain undetermined. This proposal takes advantage of a mammalian system in which these questions can be directly addressed. Much is already known about the electrical activity of the rat neurohypophysis and the subsequent release of its peptide hormones has been well characterized. It is now uniquely possible to prepare isolated nerve terminals from this neuroendocrine structure which respond to depolarization by releasing identified peptides via Ca2+ -dependent exocytosis. Recent studies have shown that release from the neurohypophysis is regulated by specific patterns of electrical activity. Thus these nerve terminals have all the properties necessary to analyze in detail the process of depolarization-secretion coupling. We propose to study, using patch-clamp and biochemical methodology, the electrophysiology of identified, in terms of peptide secreted, nerve terminals in conjunction with their differential release of neurohormones. In particular we propose to characterize in detail the Ca2+ channels found at these nerve terminals and to determine which are important for the release of vasopressin vs oxytocin. Furthermore, we will look for possible intraterminal sites of Ca2+ action leading to the exocytotic secretion of these neuroactive substances. Elucidation of the molecular mechanisms underlying such interactions would represent a major advance in the understanding of how neuronal communication is regulated.