NEURAL INTEGRATION AT AIRWAY PARASYMPATHETIC GANGLIA

气道副交感神经节的神经整合

• 批准号: 3473847
• 负责人: ALLEN C MYERS
• 金额: $ 10.77万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3473847
• 关键词: action potentials; adrenergic receptor; afferent nerve; alpha adrenergic agent; beta adrenergic agent; bronchomotion; bronchus; capsaicin; cell membrane; cholinergic receptors; guinea pigs; human tissue; innervation; membrane potentials; microelectrodes; muscarinic receptor; neural transmission; neuropharmacology; neurophysiology; paraganglia; parasympathetic nervous system; respiratory airway volume; substance P; synapses; tachykinin; tissue /cell culture

Parasympathetic nerves provide the dominant neural control of airway caliber; dysfunction of this pathway may be associated with airway disease. In the parasympathetic nerve pathway, ganglion neurons, located in the airway wall, limit preganglionic signals emanating from the central nervous system. The objectives of this proposal are to develop an understanding of how the intrinsic properties of parasympathetic ganglion neurons serve to filter or integrate excitatory signals, and how the sensory and sympathetic nervous system contribute to this integration. Regulation of guinea pig and human bronchial parasympathetic nerve activity will be investigated using in vitro microelectrode recording techniques. The first aim will be to determine what membrane properties of guinea pig bronchial ganglion neurons affect the output from these ganglia; included in this aim is the determination of the role muscarinic receptor activation plays in regulating synaptic transmission. The second aim will be to determine the role sensory nerves and tachykinins play in regulating synaptic transmission in guinea pig bronchial ganglia. The third goal will be to determine the effects of alpha- and beta-adrenergic receptor agonists, as well as the effects of sympathetic nerve stimulation, have on synaptic transmission in guinea bronchial ganglia. Lastly, experiments will be performed on human bronchial ganglion neurons to determine active and passive membrane properties, and the presence and function of muscarinic, tachykinin, and adrenergic receptors using techniques developed with the guinea pig model. In addition, the presence of tachykinin-containing sensory fibers in human ganglia will be indirectly determined by monitoring changes in membrane properties during application of capsaicin, which releases tachykinins from sensory nerve terminals. These studies will provide direct information on the physiological mechanisms that regulate transmission through airway parasympathetic ganglia. Such information may provide important new insights into the role that the nervous system may have in the pathophysiology of airway diseases such as bronchial asthma.

副交感神经提供了气道的主要神经控制 口径;该途径的功能障碍可能与气道有关 疾病。在副交感神经途径中，神经神经元位于 在气道墙中，限制从 中枢神经系统。该提议的目标是发展 了解副交感神经的内在特性 神经节神经元用于过滤或整合兴奋信号，并且 感官和交感神经系统如何贡献 一体化。豚鼠和人支气管的调节 副交感神经活性将使用体外研究 微电极记录技术。第一个目的是确定 豚鼠支气管神经节神经元的膜特性影响 这些神经节的产量；这个目标包括决心 毒蕈碱受体激活在调节突触中的作用 传播。第二个目标是确定角色感官 神经和旋转金蛋白在调节突触传播方面发挥作用 豚鼠支气管神经节。第三个目标是确定 α-和β-肾上腺素能受体激动剂以及 交感神经刺激的影响，对突触传播 在几内亚支气管神经节中。最后，将在 人支气管神经节神经元以确定主动和被动 膜特性以及​​毒蕈碱的存在和功能， 速蛋白和肾上腺素能受体使用与该技术一起开发的技术 豚鼠模型。另外，存在含他的速素的存在 人神经节中的感觉纤维将间接确定 在应用过程中监视膜特性的变化 辣椒素，可从感觉神经末端释放速素。 这些研究将提供有关生理的直接信息 通过气道副交感神经来调节传播的机制 神经节。这样的信息可能会为此提供重要的新见解 神经系统在气道的病理生理中可能具有的作用 支气管哮喘等疾病。