MODULATION & REGULATION OF NEURONAL ACH RECEPTORS

神经元的调制和突触调节信息 烟碱型乙酰胆碱受体(AChRs)处于原始阶段。 特别令人感兴趣的是神经元AChRs的调制 神经肽，如P物质，因为多肽共存 与经典神经递质共同存在于中枢和中枢神经 外周神经元，受体调节的机制 多肽具有普遍的重要性。除了短期内 神经元ACh反应的调制、特性和 AChRs的分布可能受突触发生的调节。我们会 此外，还考察了突触前输入对调节的影响 递质敏感性和神经元AChR通道。 我们的第一个目标是表征ACh的敏感性以及 胚胎单个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。 这些研究既使用了宏观的ACh诱发电流，也使用了单个 并为拟议的研究提供了一个框架 多肽对乙酰胆碱受体的调节及其在突触后的调节 队形。我们将继续我们的初步研究，以了解 磷酸化在神经元乙酰胆碱受体多肽调节中的作用 结合生理和生化方法。我们会 测量细胞和膜片中的ACh诱发电流 在激活或抑制特定的激酶之后。这些数据 将与第二信使上的多肽效应进行比较 新陈代谢。最后，我们将检查潜在的生理 乙酰胆碱受体特性的调控及其调控作用 神经交感神经元。总括而言，拟议的研究 应更好地界定糖尿病的生理生化机制 ACHR的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.