Roles of peripheral and central respiratory chemoreceptors in inbred rat strains

外周和中枢呼吸化学感受器在近交系大鼠品系中的作用

• 批准号: 8515505
• 负责人: Matthew Robert Hodges
• 金额: $ 22.58万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8515505
• 关键词: Acidosis; Acute; Address; Adult; Affect; Attention; Biological Models; Blood gas; Brain; Brain Stem; Breathing; Carbon Dioxide; Carotid Body; Cell Nucleus; Chemoreceptors; Dahl Hypertensive Rats; Data; Dependence; Development; Disease; Dopamine; Environmental air flow; Exercise; Exhibits; Functional disorder; Future; Genetic Determinism; Genomics; Goals; High Pressure Liquid Chromatography; Homeostasis; Human; Hypoxia; In Vitro; Inbred Strains Rats; Inbreeding; Individual; Instruction; Investigation; Lesion; Light; Lung diseases; Maintenance; Measures; Microdialysis; Modeling; Monoamine Oxidase A; Neuromodulator; Neurons; Norepinephrine; Peripheral; Proteins; Rat Strains; Rattus; Recovery; Regulation; Relative (related person); Rest; Role; Selective Serotonin Reuptake Inhibitor; Serotonin; Signal Transduction Pathway; Sleep; Slice; Solutions; Sudden infant death syndrome; Syndrome; Tissues; Transgenic Organisms; Update; Variant; Wakefulness; design; dopamine transporter; extracellular; human disease; in vivo; inhibitor/antagonist; insight; neuroregulation; pH Homeostasis; patch clamp; pup; research study; respiratory; response; reuptake; salt sensitive; sensory feedback

Acute adjustments in ventilation represent a powerful homeostatic mechanism for the maintenance of arterial and/or brain P02, PC02 and pH. Sensory feedback to the ventilatory control centers occurs via peripheral and central chemoreceptors, but there are several unresolved questions regarding the mechanisms and relative importance of specific subpopulations of neurons thought to act as central C02/pH chemoreceptors. What confers upon select neurons the intrinsic ability to "sense" pH? What are the signal transduction pathways for pH? Which neurons perform this task? Under which circumstances are they important (sleep wakefulness)? The overall goals of this proposal are to address some of these questions regarding central chemoreception by taking advantage of unique inbred rat strains with inherent, and large differences in C02 sensitivity; the Brown Nonway (BN: low responder) and Dahl Salt-sensitive (SS: high responder) rats. First, we will determine if the deficit in C02 sensitivity in BN rats is due to decreased cellular C02/pH sensitivity of individual chemosensitive neurons in vitro, which will be aided by the development of transgenic rats expressing fluorescent proteins in select neuron pools for direct patch clamp recordings. We will also determine the relative effects of creating focal acidosis in brainstem regions harboring these neuronal subpopulations in BN and SS rats in vivo. Finally, our preliminary data suggests that deficits in multiple neuromodulators in the brainstem may contribute to the blunted C02 sensitivity in the BN rats, and thus we will determine whether if augmenting these neuromodulators individually or collectively can restore C02 sensitivity in the BN rat. The data obtained from these unique rat strains will provide significant insights into the mechanisms and relative importance of specific chemoreceptor subpopulations in regulating eupneic ventilation and ventilatory C02 sensitivity. They will also provide insights into respiratory-related diseases, and provide a framework for future genomic investigations aimed at identifying the genetic determinants and the unique cellular mechanisms by which central chemoreception occurs.

急性通气调节是维持动脉血流稳定的一种强有力的内稳态机制