REGULATION OF NEURAL ACETYLCHOLINE RECEPTORS

除了能够将化学信号转化为 电反应，神经递质门控离子通道，它们 是动态的分子实体，受制于其 在广泛的时间范围内的响应能力。这次会议的重点是 这份提案中描述的实验是关于 调节PC12细胞的神经乙酰胆碱受体(AcChR)， 克隆性交感细胞系。激动剂的动力学性质- 介导性脱敏将通过钠内流进行检查 受体活性的测量。有没有可能 磷酸化-去磷酸化反应参与了 长效脱敏的研究进展 通过缓慢发作和恢复率，将通过获得 同时测量AcChR的范围 磷酸化。一种定量测定PC12 nAcChRs的结合试验 将开发细胞来检查失活、 激动剂诱导的产生不可逆免疫的过程 在渗透率响应中，涉及到表面的快速损失 感受器。停用和失活之间的关系 参与脱敏的受体状态将通过 对每一种影响的动力学分析 不同胆碱能拮抗剂的作用。其他人的角色 突触成分既包括细胞外的P物质，也包括 细胞内，如钙和cAMP，在进一步调节这些 激动剂介导的过程也将由相同的 生化技术。 通过考察短期和长期监管机制 激动剂和其他突触成分对nAcChR的影响 拟议的研究将有助于评估 突触后调节突触效能的机制。一个 更好地理解这些过程将有助于了解 大脑最显著的特性是：它有能力 由经验决定的。

In addition to their ability to convert chemical signals into electrical responses, neurotransmitter-gated ion channels, they are dynamic molecular entities, subject to regulation of their responsiveness over a wide temporal range. The focus of the experiments described in this proposal is on the mechanisms that regulate the neural acetylcholine receptor (AcChR) of PC12 cells, a clonal sympathetic cell line. The kinetic properties of agonist- mediated desensitization will be examined by sodium influx measurements of receptor activity. The possibility that phosphorylation-dephosphorylation reactions are involved in the development of long lasting desensitization that is characterized by slow onset and recovery rates, will be investigated by obtaining measurements, in parallel, of the extent of AcChR phosphorylation. A binding assay to quantitate nAcChRs of PC12 cells will be developed to examine whether deactivation, an agonist-induced process that produces an irreversible dimunution of the permeability response, involves a rapid loss of surface receptors. The relationship between deactivation and the receptor states involved in desensitization will be examined by kinetic analysis of the effects on the rates of each of these processes by different cholinergic antagonists. The role of other synaptic components both extracellular, e.g. substance P, and intracellular, e.g. Ca2+ and cAMP, in modulating further these agonist-mediated processes will also be evaluated by the same biochemical techniques. By examining the mechanisms of short- and long-term regulation of nAcChR by agonists and other synaptic components, the proposed studies will aid in evaluating the possible role of postsynaptic mechanisms in modulating synaptic efficacy. A better understanding of these processes will shed light on one of the most remarkable properties of the brain: its ability to be regulated by experience.