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Molecular mechanisms for olfactory signal transduction

嗅觉信号转导的分子机制

基本信息

批准号：
14380376
负责人：
KURAHASHI Takashi
金额：
$ 9.02万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

Spike discharges of single olfactory receptor cells (ORCs) were recorded with the whole-cell patch clamp method applied to the slice preparation. In parallel, activities of transduction channels were measured under the voltage-clamp condition. Current injection induced repetitive discharges. The firing frequency was dependent on the amount of injected current, showing saturation. When cells ware stimulated by odorants, 54 out of 306 cells exhibited inward currents in response to cineole under the voltage-clamp condition (holding potential =-60 mV). The amplitude of the inward current was dependent on the stimulus period, reflecting the time-integration for the stimulus dose. The dose-response relation could be fitted by the Hill equation. Under the current-clamp condition, odorants induced repetitive spikes. In those cells spike frequency was dose-dependent, expressing saturation similar to the result obtained by current injection. Since both transduction channel and spike generative steps expressed saturation in their dose dependences, we explored what step(s) actually determines saturation in ORCs' signaling processes. By examining dose-response relations of both the current and spikes in the same cells, saturating dose was found to be dependent largely on that of the transduction step. This suggests that the dynamic range is strongly influenced by the transduction system. A simple model derived from the non-linearity of the membrane could explain that the steepness of the depolarization-concentration curve became bigger as Hill coefficient of the transduction channel was increased. In addition, it was speculated that a critical level of dynamic range was, at least in part, modified by the membrane non-linearity.In addition we made experiments on identifying second messenger mediating olfactory transduction, mechanisms for cross-adaptation and some physiological measurements from human subjects regarding olfactory perception.

利用全细胞膜片钳法记录单个嗅觉受体细胞（ORCs）的Spike放电。同时，在电压箝位条件下测量了转导通道的活性。电流注入诱导重复放电。放电频率随注入电流的大小而变化，呈现饱和状态。当细胞受到气味刺激时，在电压箝位条件下（保持电位=-60 mV）， 306个细胞中有54个细胞表现出向内电流响应桉叶脑。向内电流的振幅与刺激周期有关，反映了刺激剂量的时间积分。剂量-反应关系可用希尔方程拟合。在电流箝位条件下，气味诱发重复尖峰。在这些细胞中，峰值频率是剂量依赖性的，表达与电流注射相似的饱和结果。由于转导通道和尖峰生成步骤都在剂量依赖性中表达饱和，因此我们探索了哪些步骤实际上决定了ORCs信号过程中的饱和。通过检查同一细胞中电流和峰值的剂量-反应关系，发现饱和剂量在很大程度上依赖于转导步骤。这表明动态范围受传导系统的强烈影响。由膜的非线性推导出一个简单的模型，可以解释当转导通道的希尔系数增大时，去极化-浓度曲线的陡度增大。此外，我们还推测，至少在一定程度上，薄膜非线性改变了动态范围的临界水平。此外，我们还进行了识别第二信使介导的嗅觉转导、交叉适应机制和一些人类嗅觉感知生理测量的实验。