Airway Sensory Neuroexcitability

描述（由申请人提供）：呼吸系统中绝大多数感觉神经是支气管肺c纤维。这些神经分布在整个支气管肺系统。这些神经的激活可导致刺激感和反射，包括非生产性咳嗽、粘液分泌增加、血管扩张和支气管痉挛。它们在健康的肺中通常是安静的，但可以被有害的刺激和与气道炎症相关的过程激活，包括pH值降低和各种炎症介质的存在。因此，它们被设计为气道防御系统的一部分，但当炎症变成慢性时，它们的过度激活可能会导致气道疾病的症状和病理生理。尽管支气管肺c -纤维在健康和疾病中的相关性，但我们对肺中c -纤维表型、它们的精确分布和它们的激活机制的知识基础仍存在很大差距。在目前的建议实验概述，旨在提供更详细的信息对不同表型的支气管肺c -纤维。我们将对肺内c纤维的分布提供新的见解。此外，我们的研究将增加关于神经营养素，炎症介质和质子导致肺内神经末梢电兴奋性和动作电位放电变化的生物物理机制的新知识。为了实现我们的目标，我们将结合解剖学和各种电生理技术，使我们能够以最先进的方式解决我们的假设。

DESCRIPTION (provided by applicant): The vast majority of sensory nerves in the respiratory system are bronchopulmonary C-fibers. These nerves are distributed throughout the bronchopulmonary system. Activation of these nerves can lead to sensation of irritation and reflexes including nonproductive cough, increases in mucus secretion, vasodilatation, and bronchospasm. They are typically quiet in a healthy lung, but can be activated by noxious stimuli and processes associated with airway inflammation including decreases in pH and the presence of various inflammatory mediators. They are thus designed as part of an airway defense system, but when the inflammation becomes chronic, their excessive activation likely contributes to the symptoms and pathophysiology of airway disease. The relevance of bronchopulmonary C-fibers in health and disease notwithstanding, there is a large gap in our knowledge base regarding C-fiber phenotypes in the lungs, their precise distribution, and the mechanisms of their activation. In the present proposal experiments are outlined that are aimed at providing more detailed information on the distinct phenotypes of bronchopulmonary C-fibers. We will provide new insights into the C-fiber distribution within the lungs. In addition our studies will add new knowledge regarding the biophysical mechanisms by which neurotrophins, inflammatory mediators, and protons lead to changes in electrical excitability and action potential discharge at nerve terminals within the lungs. To accomplish our aims we will bring to bear a combination of anatomical and various electrophysiological techniques that allow us to address our hypotheses in a state-of-the-art fashion.