MODULATION & REGULATION OF NEURONAL ACH RECEPTORS

关于神经元的调制和突触调节的信息 烟碱乙酰胆碱受体（AChRs）处于原始阶段。 特别令人感兴趣的是神经元乙酰胆碱受体的调节， 神经肽，如P物质。由于肽共存 与经典的神经递质是共同的， 外周神经元，受体调节机制， 肽具有普遍的重要性。 除了短期 调节神经元ACh反应，性质和 AChR的分布可能受突触发生的调节。 我们将 并探讨了突触前输入在调节中的作用 神经递质敏感性和神经AChR通道。 我们的第一个目标是表征乙酰胆碱的敏感性，以及 胚胎乙酰胆碱受体的电导和动力学 腰交感神经元在突触发生前被移除。 这些研究使用宏观乙酰胆碱诱发电流以及单个 通道记录，并为拟议的研究提供框架， 肽对乙酰胆碱受体的调节及其在突触后的调节 阵 我们会继续初步研究 神经元乙酰胆碱受体的肽调节中的磷酸化 结合生理学和生物化学方法。 我们将 测量细胞和膜斑中乙酰胆碱引起的电流 激活或抑制特定的激酶。 这些数据 将与肽对第二信使的影响进行比较 新陈代谢. 最后，我们将研究潜在的生理 AChR特性的调节作用 受支配的交感神经元 总之，拟议的研究 应该更好地定义的生理和生化机制， AChR调节以及该受体的突触调节 对中枢和外周的信号转导至关重要 突触

Information on the modulation and synaptic regulation of neuronal nicotinic acetylcholine receptors (AChRs) is at a primitive stage. Of particular interest is the modulation of neuronal AChRs by neural peptides, such as substance P. Since peptide co-existence with classical neurotransmitters is common to both central and peripheral neurons, the mechanism of receptor modulation by peptides is of general importance. In addition to the short term modulation of neuronal ACh responses, the properties and distribution of AChRs may be regulated by synaptogenesis. We will also examine the influence of presynaptic input in the regulation of transmitter sensitivity and neuronal AChR channels. Our first aim is to characterize the ACh sensitivity as well as the conductance and kinetics of individual AchRs of embryonic lumbar sympathetic neurons removed just prior to synaptogenesis. These studies use macroscopic ACh-evoked current as well as single channel recording and provide a framework for proposed studies of AChR modulation by peptides and their regulation following synapse formation. We will pursue our initial studies of the role of phosphorylation in peptide modulation of neuronal AChRs by combining physiological and biochemical approaches. We will measure ACh-elicited currents in cells and membrane patches following activation or inhibition of specific kinases. These data will be compared with peptide effects on second messenger metabolism. Finally, we will examine the potential physiological role of modulation and the regulation of AChR properties in innervated sympathetic neurons. In sum, the proposed studies should better define the physiology and biochemical mechanism of AChR modulation as well as the synaptic regulation of this receptor critical to signal transduction at central as well as peripheral synapses.