Intermittent hypoxia and carotid body activity

描述（由申请人提供）： 本项目的总体目标是确定慢性疾病 间歇性缺氧（CIH）影响颈动脉体的氧感受能力。 这一建议是基于我们的初步数据表明：a）CIH 增强颈动脉体对缺氧的感觉反应， 基线感觉活动的延长激活类似于 呼吸运动输出中的长时程易化（LTF）现象; B）5- HT受体阻滞剂阻止感觉放电中的LTF，但不能增强感觉放电中的LTF。 低氧敏感性;和c）可比较的持续低氧（SH）持续时间 既不增强对缺氧的反应，也不诱导感觉LTF 放电这些观察结果表明：1）缺氧的发作模式 在影响颈动脉体功能方面比持续缺氧更有效;以及 2)CIH影响颈动脉缺氧敏感性的机制 身体似乎不同于那些诱导LTF的基线活动。的 目前的建议测试两个主要假设：1）CIH诱导的增加， 颈动脉体的缺氧敏感性涉及颈内动脉的改变， 血管球细胞中钙浓度稳态和/或下调 抑制性递质和/或血管球细胞数量增加;和2）5- HT机制对于CIH诱导的LTF在感觉放电中的作用至关重要。 颈动脉体目的1中的实验定义了有助于CIH诱导的因素。 对颈动脉中LTF诱导的敏感性增加 身体在目标2中提出的实验，测试是否改变内部 血管球细胞中钙浓度稳态，和/或下调 抑制性神经递质如一氧化氮（NO），和/或 血管球细胞（假定的O2敏感细胞）的数量有助于 颈动脉体的化学敏感性增强。在目标3中，我们将测试 认为5-HT依赖性机制在LTF诱导中起关键作用 在颈动脉体。目的4中的实验确定CIH诱导的 缺氧敏感性和LTF的基线感觉活动的增加， 颈动脉体转化为通气量的变化。这个项目是 与项目18、14、19、16和20主题相关。此外还 来自Katz、Kunze、Dick和Kumar博士的协作互动。 由此导出的解释性数据 该项目将被纳入数学模型利用核心9007 设施

DESCRIPTION (provided by applicant): The overall goal of this project is to define the mechanisms by which chronic intermittent hypoxia (CIH) affects O2 sensing ability of the carotid body. This proposal is based on our preliminary data suggesting that: a) CIH enhances the sensory response of the carotid body to hypoxia and induces prolonged activation of the baseline sensory activity resembling the phenomenon of long-term facilitation (LTF) in respiratory motor output; b) 5- HT receptor blockers prevent LTF in the sensory discharge but not the enhanced hypoxic sensitivity; and c) comparable duration of sustained hypoxia (SH) neither enhances the response to hypoxia nor induces LTF in the sensory discharge. These observations indicate that: 1) episodic pattern of hypoxia is more potent than continuous hypoxia in affecting carotid body function; and 2) the mechanisms by which CIH affects the hypoxic sensitivity of the carotid body seem to differ from those that induce LTF in the baseline activity. The current proposal tests two primary hypotheses: 1) the CIH-induced increase in hypoxic sensitivity of the carotid body involves alterations in internal calcium concentration homeostasis in glomus cells and/or down regulation of inhibitory transmitter(s) and/or increase in number of glomus cells; and 2) 5- HT mechanisms are critical for CIH-induced LTF in the sensory discharge in the carotid body. Experiments in Aim 1 define the factors that contribute to CIH-induced heightened sensitivity and to the induction of LTF in the carotid body. Experiments proposed in Aim 2, test whether alterations in internal calcium concentration homeostasis in glomus cells, and/or down-regulation of inhibitory neurotransmitters such as nitric oxide (NO), and/or an increase in the number of glomus cells (putative O2 sensing cells) contribute to the heightened chemosensitivity of the carotid body. In Aim 3, we will test the idea that 5-HT dependent mechanisms play a critical role in induction of LTF in the carotid body. Experiments in Aim 4 determine whether CIH-induced increases in hypoxic sensitivity and LTF in baseline sensory activity of the carotid body are translated to changes in ventilation. This project is thematically linked to Projects 18, 14, 19, 16, and 20. In addition, it has collaborative interactions from Drs. Katz, Kunze, Dick, and Kumar. The ventilatory data derived from this project will be incorporated into mathematical model utilizing Core 9007 facilities.