SYNAPTIC PHYSIOLOGY

这项建议的目的是汇集一个多学科 一组研究新的或知之甚少的Ca 2+内流的研究者 途径，这些途径是如何调节的， 它们控制的过程（即突触传递/分泌）。通过 结合各种实验技术，包括分子 生物学、生物化学、电生理学和[Ca 2 +]i测量，我们 希望能帮助我们进步我们希望能召集一群 具有相似兴趣和目标，但使用各种 不同准备工作中的技术将帮助每个人 项目，并提供协同作用时无法单独工作。 在项目1中-米勒博士将研究新型钙通道（α 1 E型） 在他的实验室克隆（以及其他）。找到此通道的消息 在整个神经系统中大量存在，但功能性通道 仅在几个位置（即小脑）发现，甚至 在那里，他们是罕见的。对这种钙通道的更深入研究包括 计划定位和功能表达。有可能 这些通道还没有使用标准的 电生理程序，因为它们优先定位 到突触 在项目2中-绿色博士将研究PC 12细胞中的神经元ACh受体。 详细研究的药理学和生理特性的 这些受体是计划的，重点是它们的Ca 2+渗透性。 此外，这些受体的调节和亚基组装将 被研究。确定亚基组成的实验将 继续我们的目标是更好地了解神经元乙酰胆碱 受体多样性的实现和这些受体在 神经系统 在项目3中，Fox博士将研究Ca 2+进入和 分泌物刺激后膜修复的研究是 计划好了ACh受体的激活对 将研究分泌。对刺激的透彻理解- 分泌偶联和膜再循环对于一个完整的 了解释放过程。

The objective of this proposal is to bring together a multidisciplinary group of investigators to study novel or poorly understood Ca2+ influx pathways, how these pathways are regulated and the physiological processes they control (i.e. synaptic transmission/ secretion). By combining a variety of experimental techniques including molecular biology, biochemistry, electrophysiology and [Ca2+]i measurements, we hope to aid our progress. We expect that bringing together a group of investigators with similar interests and goals but who use a variety of techniques in different preparations will aid each of the individual projects and provide a synergy not available when working alone. In project 1 - Dr. Miller will study novel Ca channels (type alpha1E) cloned in his lab (as well as others). Message for this channel is found in abundance throughout the nervous system, but functional channels have only been found in a couple of locations (i.e. cerebellum) and even there, they are rare. More in-depth studies of this Ca channel including localization and functional expression are planned. It is possible that these channels have not been identified using standard electrophysiological procedures because they are preferentially localized to synapses. In project 2 - Dr. Green will study neuronal ACh receptors in PC12 cells. Detailed studies of the pharmacological and physiological properties of these receptors are planned, with emphasis on their Ca2+ permeability. In addition, regulation and the subunit assembly of these receptors will be studied. Experiments to determine the subunit composition will continue. The goal is to gain a greater understanding of how neuronal ACh receptor diversity is achieved and the role played by these receptors in the nervous system. In project 3 - Dr. Fox will study the relationship between Ca2+ entry and secretion. Studies of membrane retrieval following stimulation are planned. The contribution made by activation of ACh receptors to secretion will be investigated. A thorough understanding of stimulus- secretion coupling and membrane recycling are essential for a complete understanding of the release process.