HEART ATRIAL MUSCARINIC RECEPTOR

M_2型乙酰胆碱受体亚型参与调节 由副交感神经系统控制心跳，这是很有趣的 作为抗心律失常药物的可能靶点。的长期目标是 这一建议是为了了解m2受体的分子机制。 尽可能详细的信号转导。重组M2 在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 研究结构/功能的配基结合和动力学方法 受体氨基酸与发展定量关系的研究 描述受体与配体结合方式的机制和 情侣对磷脂酰肌醇代谢的刺激和抑制 阵营的形成。重组蛋白也可以从 用于生物物理研究的足够数量的过表达细胞系 如远紫外圆二向色性和傅里叶变换红外 光谱分析受体结构。这些研究应该 有助于我们理解M2受体的结构和机制。 M_2受体信号转导的数量 透视并可能导致更合理的设计更有效 抗心律失常药。

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.