SYNAPTIC PHYSIOLOGY

这项提议的目标是将一个多学科的 一组研究人员将研究新的或鲜为人知的钙离子内流 通路，这些通路是如何调节的，以及生理上的 它们控制的过程(即突触传递/分泌)。通过 结合了各种实验技术，包括分子 生物学、生物化学、电生理学和[Ca~(2+)]i测量 希望对我们的进步有所帮助。我们预计，将一群 调查人员有相似的兴趣和目标，但使用不同的 不同的准备技术对每个人都有帮助 项目并提供单独工作时所不具备的协同效应。 在项目1中，米勒博士将研究新的钙通道(Alpha1E型) 在他的实验室(以及其他实验室)克隆的。找到此频道的消息 在神经系统中大量存在，但功能通道 仅在几个位置(即小脑)发现，甚至 在那里，它们是稀有的。对这种钙通道的更深入的研究包括 计划本地化和功能表达。有可能是 这些通道尚未使用标准进行识别 电生理程序，因为它们优先定位于 通向突触。 在项目2中，格林博士将研究PC12细胞中的神经元ACh受体。 对其药理和生理特性的详细研究 这些受体是有计划的，重点是它们的钙离子渗透性。 此外，这些受体的调节和亚单位组装将 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如何疼痛 受体的多样性是实现的，这些受体在 神经系统。 在项目3中，福克斯博士将研究钙离子进入和 分泌物。电刺激后膜恢复的研究 有计划的。ACh受体激活对血管紧张素转换酶活性的影响 将对分泌物进行调查。对刺激的透彻理解-- 分泌偶联和膜循环对于一个完整的 了解发布流程。

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.