GENERAL ANESTHETIC MECHANISMS IN EXCITABLE MEMBRANES

这个项目的目的是研究分子 全麻药对配体门控离子的作用机制 频道。尽管许多调查人员进行了数十年的研究，但 全身麻醉药产生无意识的机制 都是未知的。可激发膜的离子通道一般和 尤其是配基门控离子通道可能是 麻醉药。然而，这些药物是否直接作用于 这些膜蛋白或间接发挥它们的作用， 通过细胞膜的脂质双层，目前还不清楚。 单通道记录的电生理技术 提供有关离子通道行为的直接信息，请访问 分子水平，非常适合于机理研究 毒品行为的证据。我们将使用传统的单通道 记录技术和快速药物检测的新方法 申请。挥发性麻醉药的作用(如： 异氟醚)、巴比妥酸盐(如戊巴比妥)和其他 配基门控离子通道上的麻醉药(如氯胺酮) (乙酰胆碱受体通道，NMDA激活通道，GABA 受体通道和钙激活钾通道)将 接受检查。麻醉作用模式的充分性(例如 膜流动性、通道阻断和变构结合) 测试过。选择的麻醉剂和离子通道的种类 允许在麻醉剂离子通道中搜索共性 互动。长期目标是区别对待 麻醉作用的相互竞争的理论。

This aim of this project is to investigate the molecular mechanisms of action of general anesthetics on ligand-gated ion channels. Despite decades of study by many investigators, the mechanisms by which general anesthetics produce unconsciousness are unknown. Ion channels of excitable membranes in general and ligand-gated ion channels in particular are likely "targets" of anesthetic drugs. However, whether the drugs act directly on these membrane proteins or exert their effects indirectly, through the lipid bilayer of the cell membrane, remains unclear. The electrophysiological technique of single channel recording provides direct information about the behavior of ion channels at the molecular level and is well suited to the study of mechanisms of drug action. We will use conventional single channel recording techniques and a novel method for rapid drug application. The effects of volatile anesthetics (e.g. isoflurane), barbiturates (e.g. pentobarbital) and other anesthetics (e.g. ketamine) on ligand-gated ion channels (acetlycholine receptor-channels, NMDA-activated channels , GABA receptor-channels and calcium-activated potassium channels) will be examined. The adequacy of models of anesthetic action (e.g. membrane fluidity, channel block and allosteric binding) will be tested. The variety of anesthetics and ion channels chosen permits a search for generalities in anesthetic-ion channel interactions. The long term goal is to discriminate among competing theories of anesthetic action.