CHEMOTRANSDUCTION IN THE CAROTID BODY

颈动脉体内的化学转导

• 批准号: 2226976
• 负责人: ROBERT Schaefer FITZGERALD
• 金额: $ 26.39万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1997-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2226976
• 关键词: acidosis; biological signal transduction; carotid body; cats; cholinergic agents; dopamine; dopamine receptor; high performance liquid chromatography; hypercapnia; hypoxia; immunocytochemistry; laboratory rabbit; membrane potentials; muscarinic receptor; neural transmission; neurochemistry; neuropeptide receptor; neuropharmacology; neurotransmitters; nicotinic receptors; perfusion; potassium channel; voltage /patch clamp

DESCRIPTION: (Adapted from the applicant's abstract and Specific Aims.) The broad objectives of this application are to gain deeper insight into the mechanisms operating during the carotid body's (cb) chemotransduction of hypoxia, hypercapnia, and acidosis into increased neural activity recordable in the carotid sinus nerve. On the assumption that (a) the essential chemotransductive unit consists of the Type I cell and the apposed neuron, (b) that hypoxia depolarizes the Type I cell provoking the release of neuroagent(s) which bind to a receptor(s) on the apposed neuron, and (c) this initiates processes responsible for the recordable action potentials in the carotid sinus nerve, two questions can be asked: (1) How is the Type I cell depolarized so as to release the neuroagents? (2) What are the essential excitatory and inhibitory neuroagents in the cat and how are they managed? This application addresses the second question.Five areas of research are proposed, each containing focused hypotheses to be tested: (1) Analyze the venous effluent from the in situ cat carotid body for neurotransmitters (Are those released during hypercapnia the same as those released during hypoxia?); (2) Identify the cb's excitatory and inhibitory neurotransmitters and their pharmacological interaction (Does the cb respond more to hypoxia in the presence of an M2 receptor blocker?); (3) Determine the presence and location of specific neurotransmitter receptors (Is there a neuronal nicotinic receptor on the dendrite apposed Type I cell?); (4) determine the effect of cholinergic agonists and dopamine on membrane potential and potassium channels of the Type I cells (What does ACh do to the calcium-activated potassium current?); (5) Repeat the studies of (2) in the rabbit which responds differently from the cat. Techniques include neural recording, HPLC analysis, immunocytochemistry, and patch clamping cultured Type I cells. Better knowledge of how the cb works could perhaps allow the creation of an agent to temporarily block input from the cb.

描述：（改编自申请人的摘要和具体目标。） 该应用程序的主要目标是更深入地了解 颈动脉体 (cb) 期间的运作机制 缺氧、高碳酸血症和酸中毒的化学转导增加 颈动脉窦神经中可记录的神经活动。 上 假设 (a) 基本化学传导单元由 I 型细胞和相邻的神经元，(b) 缺氧使神经元去极化 I 型细胞激发神经剂的释放，该神经剂与 相关神经元上的受体，并且 (c) 这会启动过程 负责颈动脉窦中可记录的动作电位 神经，可以问两个问题：（1）I型细胞怎么样 去极化以释放神经毒剂？ (2) 哪些是必需的 猫的兴奋性和抑制性神经毒剂以及它们是如何产生的 管理？ 该应用程序解决了第二个问题。五个领域 提出了研究，每项都包含要测试的重点假设： (1) 分析原位猫颈动脉体的静脉流出物 神经递质（高碳酸血症期间释放的神经递质与 那些在缺氧期间释放的？）； (2) 识别cb的兴奋性和 抑制性神经递质及其药理学相互作用（Does 在存在 M2 受体的情况下，CB 对缺氧的反应更大 拦截器？）； (3)确定特定的存在和位置 神经递质受体（是否有神经元烟碱受体 树突并列的 I 型细胞？）； (4) 确定效果 胆碱能激动剂和多巴胺对膜电位和钾的影响 I 型细胞通道（ACh 对钙激活细胞有何作用） 钾电流？）； (5) 在兔子身上重复(2)的研究， 与猫的反应不同。 技术包括神经记录、 HPLC 分析、免疫细胞化学和膜片钳培养 I 型 细胞。 更好地了解CB的工作原理也许可以让 创建一个代理来暂时阻止来自 cb 的输入。