DEPOLARIZATION SECRETION COUPLING IN NERVE TERMINALS

神经递质的释放是轴突刺突侵入神经的结果 terminals. 虽然有相当多的证据表明， 神经元胞体导致Ca 2+的进入和随后的分泌 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从神经释放 终端仍然不确定。 该提案利用了 哺乳动物系统中，这些问题可以直接解决。 多 关于大鼠神经垂体的电活动， 随后释放的肽类激素 表征了 现在，制备分离的神经 神经内分泌结构的末端， 通过Ca 2+依赖性释放鉴定的肽进行去极化 胞吐作用 最近的研究表明， 神经垂体由特定的电活动模式调节。 因此，这些神经末梢具有分析所需的所有特性， 详细描述了去极化-分泌偶联的过程。 我们建议 研究，使用膜片钳和生物化学方法，电生理学 在肽分泌方面， 神经激素的不同释放。 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， 并确定哪些对血管加压素的释放重要， 催产素 此外，我们将寻找可能的终端内的网站， Ca 2+作用导致这些神经活性物质的胞吐分泌 物质. 阐明了这种现象背后的分子机制 相互作用将代表着理解如何 神经元的交流受到调节。

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.