Signal Transduction in Intrapulmonary Chemoreceptors

肺内化学感受器的信号转导

• 批准号: 7981434
• 负责人: STEVEN C HEMPLEMAN
• 金额: $ 43.97万
• 依托单位: NORTHERN ARIZONA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7981434
• 关键词: 4-Aminopyridine; ATP phosphohydrolase; Aerobic; Affect; Amiloride; Ammonium Chloride; Anesthetics; Anoxia; Apamin; Arizona; Automobile Driving; Bicarbonates; Biomedical Research; Birds; Blood flow; Breathing; Buffers; Calcium; Carbon Dioxide; Cell membrane; Characteristics; Charybdotoxin; Chemoreceptors; Complication; Coupled; Coupling; Dehydration; Dependence; Disease; Economic Inflation; Energy Metabolism; Environmental air flow; Esomeprazole; Frequencies; Future; Gases; Glyburide; H(+)-K(+)-Exchanging ATPase; Hand; Hand functions; Health; Human; Hydration status; Infusion procedures; Intracellular Transport; Intravenous; Ion Channel; Laboratories; Lactic acid; Left lung; Left pulmonary artery; Lung; Mammals; Mechanoreceptors; Medical; Membrane; Metabolic; Modeling; Na(+)-K(+)-Exchanging ATPase; Neurons; Ouabain; Oxalates; Oxygen; Pathway interactions; Patients; Pharmaceutical Preparations; Phylogenetic Analysis; Play; Potassium; Potassium Channel; Process; Production; Property; Proton-Translocating ATPases; Protons; Pulmonary Heart Disease; Pulmonary Stretch Receptors; Regulation; Research; Role; Scientist; Signal Transduction; Stimulus; Stomach; Stream; Stretching; Sulfonylurea Compounds; Testing; Tolbutamide; Training; Universities; Vertebrates; Work; anaerobic glycolysis; antiport; carbonate dehydratase; career; cost; effective therapy; experience; gadolinium chloride; graduate student; inhibitor/antagonist; interest; ion channel blocker; mind control; public health relevance; pyridine; relating to nervous system; research study; respiratory; response; sensor

DESCRIPTION (provided by applicant): We will study the cellular mechanisms of CO2 transduction in avian intrapulmonary chemoreceptors (IPC) as a model for general principles of respiratory CO2 transduction in vertebrates. We will use this research to introduce undergraduate and graduate students at Northern Arizona University to biomedical research using hands-on lab experiences and training in scientific practice. Aim I of this proposal will test whether active proton transport by v-type H+ ATPase and H+/K+-ATPase participate in pH regulation and CO2 transduction in IPC. Concanomycin A and esomeprazole will be used while recording single unit chemoreceptor responses to phasic CO2 stimuli. Aim II will test whether transient lactic acid accumulation or KATP channels play roles in IPC spike frequency adaptation (SFA), using lactate infusion and glibenclamide with single-unit recordings. Aim III will test the hypothesis that IPC share some signal transduction properties found in mammalian CO2-sensitive pulmonary stretch receptors (PSR), which would indicate a degree of phylogenetic homology between PSR and IPC. 4-amino pyridine, a fast K+ ion channel blocker shown to decrease PSR response to CO2, and gadolinium chloride, a blocker of stretch activated ion channels which impairs PSR response to lung inflation, will be studied in single-unit IPC. Aim IV will investigate the role of Na+/K+ ATPase in energizing the IPC membrane and influencing Ca++ levels via Na+/Ca++ exchange. This research will enhance understanding of respiratory chemoreceptors in general, attract and train of future scientists at NAU, and may suggest medical treatments useful for treating disorders in CO2 chemosensitivity. PUBLIC HEALTH RELEVANCE: This research investigates fundamental neural processes that detect CO2 levels in the body and send neural signals to the brain that control breathing. This is important for human health, because better understanding of respiratory CO2 chemotransduction may help develop more effective treatments and drugs for the loss of CO2 chemosensitivity, a common complication seen in patients with severe cardiopulmonary disease. The research will also be used to stimulate interest and give hands-on scientific experience to undergraduate and graduate students at Northern Arizona University interested in biomedical research careers.

描述（由申请人提供）：我们将研究鸟类肺内化学感受器（IPC）中二氧化碳转导的细胞机制，作为脊椎动物呼吸二氧化碳转导一般原理的模型。我们将利用这项研究，通过实验室实践经验和科学实践培训，向北亚利桑那大学的本科生和研究生介绍生物医学研究。该提案的目标 I 将测试 v 型 H+ ATP 酶和 H+/K+-ATP 酶的主动质子转运是否参与 IPC 中的 pH 调节和 CO2 转导。在记录单单位化学感受器对阶段性 CO2 刺激的反应时，将使用 Concanomycin A 和埃索美拉唑。 Aim II 将使用乳酸输注和格列本脲进行单单位记录，测试瞬时乳酸积累或 KATP 通道是否在 IPC 尖峰频率适应 (SFA) 中发挥作用。目标 III 将检验以下假设：IPC 具有哺乳动物 CO2 敏感肺牵张受体 (PSR) 中发现的一些信号转导特性，这表明 PSR 和 IPC 之间存在一定程度的系统发育同源性。 4-氨基吡啶（一种快速 K+ 离子通道阻断剂，可降低 PSR 对 CO2 的反应）和氯化钆（一种拉伸激活离子通道阻断剂，可削弱 PSR 对肺充气的反应）将在单机 IPC 中进行研究。 Aim IV 将研究 Na+/K+ ATP 酶在为 IPC 膜提供能量并通过 Na+/Ca++ 交换影响 Ca++ 水平方面的作用。这项研究将增强对呼吸化学感受器的总体理解，吸引和培训 NAU 的未来科学家，并可能提出可用于治疗 CO2 化学敏感性疾病的药物治疗方法。 公共健康相关性：这项研究调查了检测体内二氧化碳水平并向控制呼吸的大脑发送神经信号的基本神经过程。这对人类健康很重要，因为更好地了解呼吸二氧化碳化学转导可能有助于开发更有效的治疗方法和药物来治疗二氧化碳化学敏感性的丧失，这是严重心肺疾病患者常见的并发症。该研究还将用于激发对生物医学研究职业感兴趣的北亚利桑那大学本科生和研究生的兴趣并为其提供实践科学经验。

项目成果

Comparative embryology of the carotid body.

颈动脉体的比较胚胎学。

• 发表时间: 2013-01-01
• 影响因子: 2.3
• 作者: Hempleman, Steven C;Warburton, Stephen J
• 通讯作者: Warburton, Stephen J

Effects of aerobic and anaerobic metabolic inhibitors on avian intrapulmonary chemoreceptors.

有氧和无氧代谢抑制剂对禽肺内化学感受器的影响。

• DOI: 10.1152/ajpregu.90608.2008
• 发表时间: 2009-05-01
• 期刊: American journal of physiology. Regulatory, integrative and comparative physiology
• 作者: Jason Q. Pilarski;I. Solomon;D. Kilgore;S. Hempleman
• 通讯作者: S. Hempleman