MECHANISM OF ACTION OF VOLATILE ANESTHETICS

这项研究的长期目标是了解 挥发性麻醉剂的作用。关于波动性有多大，我们知之甚少 麻醉剂会产生可逆的无意识；我们的情况就是如此 对大体解剖学或亚细胞/分子的理解 水平。这项提议使用了分子遗传学的方法来试图理解 挥发性麻醉剂对线虫的作用机制。 我们已经鉴定出两个不协调的突变体，它们与 野生型蠕虫对最有效的挥发性物质的敏感性 麻醉剂。这些突变株UNC-79和UNC-80均表现正常 在麻醉药中，当与其他突变结合时，UNC-1、UNC-7、UNC-9或 北卡罗来纳大学-24。它们的行为表明麻醉部位发生了变化 行动。我们计划利用这些突变来了解分子本质 麻醉作用的部位。这项建议的具体目标是： 1.研究线虫麻醉反应的遗传控制 通过分离改变作用部位的额外突变 挥发性麻醉剂。 2.为了进一步确定我们最近发现的突变的特征 改变麻醉作用的部位。这将需要绘制这些 并确定它们与其他相关基因的相互作用。 最终，我们希望确定一条控制 对这些代理的回应。 3.利用转座子标签技术克隆UNC-1。我们计划 分析相应蛋白质产品的一级结构，以及 在更复杂的生物体中寻找同源蛋白质产物。这 信息将与其他人积累的数据相结合 在实验室研究UNC-79和UNC-80。

The long term goal of this study is to understand the molecular basis of action of volatile anesthetics. Little is known about how volatile anesthetics produce reversible unconsciousness; this is true of our understanding at either the gross anatomical or subcellular/molecular level. This proposal uses a molecular genetic approach to try to understand the mechanism of action of volatile anesthetics in C. elegans. We have identified two uncoordinated mutants that differ greatly from the wild type worm in their sensitivity to the most potent volatile anesthetics. These mutant strains, unc-79 and unc-80, each behave normally in anesthetics when combined with other mutations, unc-1, unc-7, unc-9, or unc-24. Their behavior indicates changes at the sites of anesthetic action. We plan to use these mutations to understand the molecular nature of the site of anesthetic action. The specific aims of this proposal are: 1. To characterize the genetic control of anesthetic response in C. elegans by isolating additional mutations which alter the site of action of volatile anesthetics. 2. To further characterize the mutations we have recently identified as altering the anesthetic site of action. This will entail mapping these genes and determining their interaction with the other involved genes. Ultimately we wish to determine a functional pathway which controls response to these agents. 3. To clone unc-1 using the transposon tagging technique. We plan to analyze the primary structure of the corresponding protein products, and search for homologous protein products in more complex organisms. This information will be combined with the data being accumulated by others studying unc-79 and unc-80 in our laboratory.