Noncompetitive Inhibition of the Acetycholine Receptor

9515330约翰逊，在所有脊椎动物中，神经肌肉连接是信息从中枢神经系统流向肌肉的关键中继点。在这些交界处终止的运动神经元释放神经递质乙酰胆碱，它扩散一小段距离与分子受体分子乙酰胆碱受体相互作用。这些关键的受体是通道孔，当被乙酰胆碱激活时，它们会打开，从而启动导致肌肉收缩的一连串事件。通过这笔赠款的资助，进行了实验以确定乙酰胆碱受体的详细结构，这些结构可以从电射线中大量获得。这种方法是定量荧光光谱的方法，这是一种研究完整乙酰胆碱受体分子结构特征的独特技术。这些实验旨在描绘抑制剂物质的特定结合部位，从而加强对这些结合部位如何随乙酰胆碱受体孔的打开和关闭而变化的理解。这项研究将极大地促进对化学物质对乙酰胆碱受体作用的分子理解。这样的理解将为这种至关重要的蛋白质如何在分子水平上发挥作用提供洞察力。研究乙酰胆碱受体的概念和实验方法将适用于在所有动物中发现的大量其他神经递质和激素受体。

9515330 Johnson The neuromuscular junction is a critical relay point in the flow of information from the central nervous system to muscles in all vertebrate animals. Motor neurons ending at these junctions release the neurotransmitter, acetylcholine, which diffuses a short distance to interact with molecular receptor molecules, the acetylcholine receptors. These critical receptors are channel pores that open when activated by acetylcholine, thereby initiating the cascade of events that leads to muscle contraction. Through funding of this grant experiments are carried out to determine the detailed structure of acetylcholine receptors, which can be obtained in large quantities from the electric ray. The approach is that of quantitative fluorescence spectroscopy, a unique technique for studying structural features of intact acetylcholine receptor molecules. The experiments are meant to delineate the specific binding sites of inhibitors substances and thus to enhance the understanding of how these bindine sites change as the acetylcholine receptor pore opens and closes. This study should significantly contribute to the development of a molecular understanding of the actions of chemicals on the acetylcholine receptor. Such understanding will provide insights into how this critically important protein functions at a molecular level. Concepts and experimental approaches developed in the study of the acetylcholine receptor will be applicable to the vast array of other neurotransmitter and hormone receptors found in all animals.