Transduction mechanism in olfactory sensory neurons

描述（由申请人提供）：本提案的长期目标是定量了解嗅觉感觉神经元（OSN）中的转导机制。目前，几乎没有任何关于转导过程中每一步的生物物理信息。这些信息对于真正理解这一过程以及最终了解其疾病状态至关重要，这在过去二十年中我们对视网膜光转导的认识取得的进展中得到了充分的证明。具体目标是： 1)研究气味物质和受体蛋白之间的相互作用，并发现气味物质受体在没有气味物质的情况下是否具有任何组成性活性。 2)了解宏观嗅觉反应背后的单一事件的本质，并观察OSN对单个气味分子的反应是否确实可检测。我们还将剖析环核苷酸门控电流和钙激活的CI电流的单一响应的贡献。 3)量化嗅觉传导过程的钙依赖性适应， 4)研究钙非依赖性的适应过程，以及GRK3，RGS2和ADMucin在嗅觉反应终止中的可能作用。 实验方法包括用吸管记录来自青蛙和小鼠的单个OSN。还将使用基因工程小鼠品系。

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.