PERIPHERAL MECHANISMS OF OLFACTORY RECEPTION

嗅觉神经元的刺激激活是由可逆的 气味物质与树突状细胞受体蛋白的相互作用 睫状膜。刺激与受体的结合随后导致 到膜去极化、动作电位产生，以及 突触传递。然而，分子事件的序列 受体激活和膜去极化残留物之间 不完全具有特征的。最新的生物化学和 在几个脊椎动物物种中有电生理证据 提示G蛋白连接的第二信使系统可能是 参与嗅觉刺激反应耦合。主要目标是 建议的研究是确定第二个受监管的刺激 斑点叉尾鱼嗅觉系统中的信使和 确定第二信使在离子事件中的作用 下层膜去极化。生化的， 将使用神经生理学和生物物理方法来 描述连接的分子和细胞机制 刺激-感受器相互作用和随后的离子事件。 生物化学实验将被用来确定 第二信使代谢和受体特异性之间的关系 入住率。G蛋白在调节第二信使中的作用 将使用生物化学方法研究分离纤毛中的新陈代谢 已建立的G蛋白效应器。这些实验结合在一起， 随着电生理和生物物理研究的重组 膜和分离的受体细胞，将被用于确定 第二信使和G蛋白在离子调节中的作用 通道和细胞内离子浓度。应用程序 将这些技术应用到一个模型系统中，在该模型系统中 交互具有很好的特性，将提供全面和 分子和细胞事件的综合描述 潜在的嗅觉信号转导。

Stimulus activation of olfactory neurons is initiated by reversible interactions of odorants with receptor proteins in the dendritic ciliary membrane. Stimulus binding to receptor subsequently leads to membrane depolarization, action potential generation, and synaptic transmission. However, the sequence of molecular events between receptor activation and membrane depolarization remains incompletely characterized. Recent bio-chemical and electrophysiological evidence in several vertebrate species has indicated that G-protein-linked second messenger systems may be involved in olfactory stimulus response coupling. The major goal of the proposed research is to identify stimulus regulated second messengers in the olfactory system of the channel catfish and to determine the role of second messengers in the ionic events underlying membrane depolarization. Biochemical, neurophysiological, and biophysical methods will be used to characterize the molecular and cellular mechanisms that link stimulus-receptor interaction and subsequent ionic events. Biochemical experiments will be used to determine the relationships between second messenger metabolism and receptor specificity and occupancy. The role of G-proteins in mediating second messenger metabolism will be studied biochemically in isolated cilia using established G-protein effectors. These experiments, in combination with electrophysiological and biophysical studies in reconstituted membranes and dissociated receptor cells, will be used to determine the roles of second messengers and G-protein in regulation of ion channels and intracellular ion concentrations. Application of these techniques to a model system in which stimulus receptor interaction is well characterized, will provide a comprehensive and integrated description of the molecular and cellular events underlying olfactory signal transduction.