CHEMOTRANSDUCTION IN THE CAROTID BODY

描述：(根据申请者的抽象和具体目标改编。) 此应用程序的广泛目标是更深入地了解 颈动脉小体(CB)的作用机制 低氧、高碳酸血症和酸中毒的化学转导增加 在颈动脉窦神经中可记录到神经活动。论 假设(A)基本的化学转导单位由 I型细胞和相反的神经元，(B)低氧去极化 I型细胞刺激神经毒剂(S)的释放，该神经毒剂与 对置神经元上的受体(S)，以及(C)这启动了 负责颈动脉窦可记录的动作电位 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)本质是什么 猫的兴奋性和抑制性神经毒剂以及它们是如何 管理？这个应用程序解决了第二个问题。 建议进行研究，每项研究都包含需要检验的重点假设： (1)分析猫原位颈动脉小体静脉流出物 神经递质(高碳酸血症期间释放的神经递质与 在低氧时释放的那些？)；(2)识别CB的兴奋性和 抑制性神经递质及其药理相互作用 在M2受体存在的情况下，CB对缺氧的反应更强 阻滞剂？)；(3)确定特定的 神经递质受体(是否存在神经性尼古丁受体 树突顶端的I型细胞？)；(4)测定 胆碱能激动剂和多巴胺对膜电位和钾的影响 I型细胞的通道(ACh对钙激活的 钾电流？)；(5)在兔体内重复(2)研究 它的反应与猫不同。技术包括神经记录， 高效液相色谱分析、免疫细胞化学和膜片钳技术 细胞。更好地了解CB的工作原理可能会使 创建代理以临时阻止来自CB的输入。

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.