ENGINEERED CHANNELS FOR STUDY OF PCP ACTION

NMDA受体结构与苯环利定(PCP)的关系 将使用表达克隆通道的技术来检查敏感性 在卵母细胞系统中，并监测表达元件的功能 使用电生理技术。我们将使用四种拼接变体， 具有已知氨基酸序列的NMDAR1受体/通道亚单位 我们已经从大鼠的大脑中分离出它们，以联系不同的 不同参数的五氯苯酚产品的结构 敏感度。特别是，我们将确定特定的角色 香料中存在或不存在的氨基酸序列 变异体在NMDA激活的特性中发挥作用 受体/通道及其相关的调节机制 五氯苯酚的活动。氨基酸序列的存在或缺失 其包括呈现拼接变体的拼接盒 在受体的电荷分布方面有很大不同 蛋白质，这些差异可能会影响五氯苯酚的作用。这个 特征的存在或不存在的后果 本课程将探讨五氯酚的脱敏作用。这项工作，这是 主要是一项试点研究，将确定这一特殊情况的用处 为调查五氯苯酚的行动做准备，并将提供 设计智能突变所需的背景信息 未来的实验。

The relationship between NMDA receptor structure and phencyclidine (PCP) sensitivity will be examined, using techniques to express cloned channels in an oocyte system, and monitoring the function of the expressed elements with electrophysiological techniques. We will use four splice variants, with known amino acid sequences, of the NMDAR1 receptor/channel subunit which we have isolated from rat brain to relate differences in the structure, of their products with differences in various parameters of PCP sensitivity. In particular, we will determine the role which particular amino acid sequences which are either present or absent in the spice variants play in the characteristics of NMDA activation of the receptor/channel and the associated modulation of receptor/channel activity by PCP. The presence or absence of the amino acid sequences which comprise the spliced cassettes render the splice variants considerably different with respect to charge distribution of the receptor protein, and these differences are likely to affect PCP actions. The consequences of the presence or absence of characteristics such as desensitization for PCP action will be explored. This work, which is primarily a pilot study, will determine the usefulness of this particular preparation for the investigation of PCP action, and will provide the background information necessary to devise intelligent mutagenesis experiments in the future.