HEART ATRIAL MUSCARINIC RECEPTOR

M2毒蕈碱型乙酰胆碱受体亚型介导调节 副交感神经系统对心跳的影响， 作为抗心律失常药物的可能靶点 的长期目标 本研究旨在了解M2受体的分子机制。 信号转导尽可能详细。 重组m2 中国仓鼠卵巢细胞中表达的受体提供了一个有用的系统 来实现这一目标。 定点诱变与 配体结合和动力学方法来检查结构/功能 受体氨基酸的关系，并开发定量 描述受体结合配体的方式的机制， 偶联刺激磷脂酰肌醇代谢和抑制 cAMP的形成。 重组蛋白还可以从以下纯化： 过量表达足够数量的细胞系用于生物物理研究 例如远紫外圆二色性和傅立叶变换红外 光谱分析受体结构。 这些研究应 有助于我们理解m2受体的结构和机制 m2毒蕈碱受体信号转导的定量 的角度，并可能导致更有效的合理设计 抗肿瘤药

The m2 muscarinic acetylcholine receptor subtype mediates the regulation of the heartbeat by the parasympathetic nervous system and is of interest as a possible target for antiarrhythmia drugs. The long-term objective of this proposal is to understand the molecular mechanism of m2 receptor signal transduction in as much detail as possible. The recombinant m2 receptor expressed in Chinese Hamster ovary cells provides a useful system to accomplish this goal. Site-directed mutagenesis is combined with ligand binding and kinetic approaches to examine structure/function relationships for receptor amino acids and to develop quantitative mechanisms describing the manner in which the receptor binds ligands and couples to stimulation of phosphatidylinositol metabolism and inhibition of cAMP formation. The recombinant protein can also be purified from overexpressing cell lines in sufficient quantities for biophysical studies such as far ultraviolet circular dichroism and Fourier transform infrared spectroscopy to analyze receptor structure. These studies should contribute to our understanding of m2 receptor structure and the mechanism of m2 muscarinic receptor signal transduction from a quantitative perspective and may result in the rational design of more effective antiarrhythmic agents.