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理解嗅觉感觉神经元（OSN）中的转导机制。目前，在转导过程中几乎没有关于每个步骤的生物物理信息。这些信息对于真正理解该过程并最终其疾病状态至关重要，这在过去二十年中关于视网膜光转导的知识的进步中得到了很好的例证。具体目的是： 1）检查气味蛋白与受体蛋白之间的相互作用，并找出在没有气味剂的情况下，气味受体是否具有任何构成活性。 2）了解宏观嗅觉响应背后的单一事件的性质，并查看OSN对单个气味分子的响应是否确实可以检测到。我们还应剖析环状核苷酸门控电流和CA激活的CI电流对单位反应的贡献。 3）量化嗅觉转导过程的CA依赖性适应 4）研究该过程的CA不依赖性适应，以及GRK3，RGS2和哲学在嗅觉响应终止中的可能作用。 实验方法涉及从青蛙和小鼠带有吸管的单个OSN记录。也将使用基因工程的鼠标线。