Transduction mechanism in olfactory sensory neurons

嗅觉感觉神经元的传导机制

• 批准号: 7064775
• 负责人: KING-WAI YAU
• 金额: $ 35.92万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7064775
• 关键词: G protein coupled receptor kinase; Rana; biological signal transduction; biophysics; calcium flux; chemoreceptors; chloride ion; electrophysiology; enzyme activity; genetically modified animals; guanosinetriphosphatase activating protein; intermolecular interaction; laboratory mouse; neural information processing; neurons; odors; olfactions; olfactory stimulus; protein kinase; receptor binding; sensory feedback; single cell analysis

DESCRIPTION (provided by applicant): The long-term objective of this proposal is to understand quantitatively the transduction mechanism in olfactory sensory neurons (OSNs). At present, there is hardly any biophysical information about each step in the transduction process. This information is crucial for truly understanding the process and ultimately its disease states, as amply exemplified in the advancements in our knowledge about retinal phototransduction in the past two decades. The specific aims are: 1) To examine the interaction between the odorant and the receptor protein, and to find out whether odorant receptors have any constitutive activity in the absence of odorants. 2) To understand the nature of the unitary event underlying the macroscopic olfactory response, and to see whether the response of an OSN to a single odorant molecule is indeed detectable. We shall also dissect the contributions of the cyclic nucleotide-gated current and the Ca-activated CI current to the unitary response. 3) To quantify Ca-dependent adaptation of the olfactory transduction process, and 4) To study Ca-independent adaptation of the process, and the possible roles of GRK3, RGS2 and phosducin in the termination of the olfactory response. The experimental approach involves recording from single OSNs from frog and mouse with a suction pipette. Genetically engineered mouse lines will also be used.

描述（由申请人提供）：该提案的长期目标是定量了解嗅觉感觉神经元（OSN）的转导机制。目前，几乎没有关于转导过程中每个步骤的生物物理信息。这些信息对于真正理解这一过程及其最终的疾病状态至关重要，过去二十年我们对视网膜光转导知识的进步充分证明了这一点。具体目标是： 1）考察气味剂与受体蛋白之间的相互作用，了解气味受体在没有气味剂的情况下是否具有组成活性。 2) 了解宏观嗅觉反应背后的单一事件的本质，并了解 OSN 对单个气味分子的反应是否确实可检测到。我们还将剖析环核苷酸门控电流和 Ca 激活 CI 电流对单一响应的贡献。 3) 量化嗅觉转导过程的 Ca 依赖性适应，以及 4) 研究该过程的Ca非依赖性适应，以及GRK3、RGS2和phosducin在嗅觉反应终止中的可能作用。 实验方法包括用吸管记录青蛙和小鼠的单个 OSN。还将使用基因工程小鼠品系。