MEMBRANE EXCITABILITY AND SECRETION FROM NERVE ENDINGS

膜兴奋性和神经末梢的分泌

• 批准号: 6469112
• 负责人: MEYER B. JACKSON
• 金额: $ 1.79万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-01-01 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6469112
• 关键词: Xenopus oocyte; action potentials; biological signal transduction; calcium flux; computer simulation; cyclic GMP; dielectric property; drug receptors; electrophysiology; endocytosis; enzyme inhibitors; exocytosis; hormone regulation /control mechanism; laboratory rat; ligands; membrane channels; nerve endings; neurohypophysis; nitric oxide; nitric oxide synthase; potassium channel; secretion; sodium channel; tissue /cell preparation; voltage /patch clamp

DESCRIPTION: The posterior pituitary is formed by nerve terminals emanating from the hypothalamus. The posterior pituitary releases two peptide hormones, vasopressin, which regulates blood circulation and renal function, and oxytocin, which regulates various reproductive functions. The nerve terminals of the posterior pituitary are unusually large, making them ideal for experimentation with patch clamp and imaging techniques. This provides a unique opportunity to investigate basic mechanisms underlying the regulation of neurosecretion. The present plan continues an investigation of membrane excitability in the posterior pituitary, emphasizing two recently discovered aspects of ion channel modulation. The first of these involves the labile gaseous signaling molecule nitric oxide (NO), which modulates ion channels in the posterior pituitary. Experiments will explore how NO and the NO signaling cascade modulate ion channels. The second involves sigma receptors, which modulate posterior pituitary ion channels in response to a number of ligands, including antipsychotic and psychotomimetic drugs. NO and sigma receptors employ novel mechanisms in the modulation of ion channels, and represent important additions to the repertoire of signaling pathways that affect electrical excitability. These mechanisms of ion channel modulation take on added significance in the context of the posterior pituitary, because they contribute to the regulation of neurosecretion. This study will examine how alterations in channel function influence action potential shape, calcium entry, and the propagation of electrical impulses through the complex terminal arborizations of the posterior pituitary. These factors influence release in profoundly different ways. Thus, this project will test basic hypotheses about how chemical signaling controls neurosecretion. Since axons generally extend over considerable distances, exhibit complex geometries, and have very large numbers of secretory specializations, these studies of the relationship between axonal geometry and ion channel modulation will have broad implications for the role of axon terminals in neural circuit function.

描述：垂体后垂体是由发出的神经终端形成的 来自下丘脑。垂体后释放两种肽激素， 加压素，调节血液循环和肾功能，以及 催产素，调节各种生殖功能。神经终端 垂体后部的大小异常大，使其非常适合 使用斑块夹和成像技术实验。这提供了独特的 调查调节的基本机制的机会 神经分泌。本计划继续调查膜 垂体后部的兴奋性，强调了两个最近发现的 离子通道调制的各个方面。其中的第一个涉及不稳定 气体信号分子一氧化氮（NO），它调节离子通道中的离子通道 后垂体。实验将探索否和否发出的信号 级联调节离子通道。第二个涉及Sigma受体， 调节垂体后离子通道，以响应许多配体， 包括抗精神病药和心理药物。否和Sigma受体 在离子通道的调制中采用新型机制，并表示 对影响的信号通路曲目的重要补充 电兴奋性。这些离子通道调制的机制采用 在后垂体的背景下增加了重要性，因为它们 有助于神经分泌的调节。这项研究将研究如何 信道功能的改变会影响动作电位形状，钙 进入，以及电动通过复合端子的传播 后垂体的树木。这些因素影响释放 深远的方式。因此，该项目将检验有关的基本假设 化学信号传导如何控制神经分泌。由于轴突通常延伸 超过距离，表现出复杂的几何形状，并且具有很大的 分泌专业的数量，这些研究 轴突几何形状和离子通道调制将对 轴突终端在神经回路功能中的作用。