CELLULAR MECHANISMS OF OLFACTION

这个项目的长期目标是确定细胞机制 嗅觉。该提案将重点放在导致以下目标的初始步骤 嗅觉：嗅觉感受器的转导和适应 细胞。 分子生物学、生物化学和生物化学的最新进展 嗅觉感受器细胞的电生理学已经确定了一些 可能参与转导的细胞内信使 气味刺激转化为电生理反应。然而，许多人 关键问题仍然没有得到回答，关于每个推定的 信使及其在产生或调节气味反应中的作用。 这些问题将通过使用膜片钳记录从 孤立的受体细胞。首先，气味诱导剂的特性 将描述转换电流的特性。所有这些激起的电流 假定的第二信使将被描述并与 气味引起的洋流。这些数据，连同对 干扰推定的药物的作用 转导机制，将确立每个人的功能 嗅觉传导中的细胞内信使。适应将是 以类似的方式学习。这些实验的一个主要优势将是 使用哺乳动物动物模型，即大鼠，这将允许直接 获得的电生理数据与生长曲线的比较 来自啮齿动物的生化和分子遗传学数据。一项额外的 力量将是一种新的方法的使用：光解激活 第二个信使和气味。 该项目将提供有关发生在 哺乳动物嗅觉感受器细胞，信息可以立即 与人类嗅觉的相关性，正如我们所展示的 小鼠嗅觉敏感度的诱导。此外，这项工作将 为相关的生理研究奠定了基础 物种对人类嗅觉感受器细胞的生理和病理影响。

The long term goal of this project is to determine the cellular mechanisms of olfaction. This proposal will focus on the initial steps leading to olfactory perception: transduction and adaptation in the olfactory receptor cells. Recent progress on the molecular biology, biochemistry, and electrophysiology of olfactory receptor cells have identified a number of intracellular messengers that may be involved in the transduction of odorous stimuli into an electrophysiological response. Nevertheless, many key questions remain unanswered regarding the importance of each putative messenger and it's role in generating or modulating odorant responses. These questions will be addressed by using patch clamp recordings from solitary receptor cells. First, the properties of the odorant-induced transduction current will be characterized. The currents evoked by all of the putative second messengers will be characterized and compared with the currents evoked by odorants. These data, together with observations on the effects of pharmacologic agents that interfere with the putative transduction mechanisms, will establish the functions of each of the intracellular messengers in olfactory transduction. Adaptation will be studied in a similar manner. A major strength of these experiments will be the use of a mammalian animal model, the rat, which will permit direct comparisons between the electrophysiological data obtained and the growing body of biochemical and molecular genetic data from rodents. An additional strength will be the use, of a novel approach: photolytically activated second messengers and odorants. This project will provide novel data about processes occurring within mammalian olfactory receptor cells, information that can have immediate relevance to human olfaction, as we have shown for induction of olfactory sensitivity in mice. In addition, this work will serve as foundation for relating physiological studies on a variety of species to the physiology and pathology of human olfactory receptor cells.