CAROTID BODY CHEMORECEPTION--MECHANISMS & DEVELOPMENT

颈动脉小体化学感受器是引起 增加通气量以应对PaO2或PHA的下降。这 反应性在出生时就很弱，在最初的几周里会增加 生活的一部分。虽然传入鼻窦神经活动与 PaO2或PHA表征良好，其转导机制和 成熟是不被理解的。球体细胞，与 传入神经末梢，是最有可能的转导部位 化疗敏感性在血管球瘤细胞破坏后被消融。然而， 球体细胞对低氧反应的电生理学研究结果 实验室和制剂之间一直不一致。为 例如，相反的证据表明，球体细胞是电性的 可兴奋和不可兴奋，且膜离子电流增加且 随着缺氧时间的延长而降低。 为了解决这些问题并了解 化疗敏感性及其发育变化，我们建议使用贴片 血管球体细胞的钳制记录和光学测量 从兔子身上急性分离出来的。我们的初步结果已经确定 我们从球体采集、膜片钳和光学记录的能力 成人和新生儿的细胞。我们已经证明了缺氧性缺氧 和组织毒性缺氧引起特定的，但相反的，改变 以球体细胞表示的电压依赖性外向电流，以及 新生血管球体细胞对这两种药物的反应缺失或减少。 提出了以下一般假设：化学转导 低氧是由氧依赖的钙结合蛋白的变化所介导的。 将解决以下问题：1)发生了哪些变化 成人肾小球的钠、钾、钙离子膜电流 细胞对低氧的反应，增加了H+，降低了能量 2)球菌胞内钙离子和pH是如何调节的 细胞和水平会随着缺氧而变化吗？3)什么变化解释了 成熟期增加的颈动脉体低氧敏感性？这个 这项工作的预期结果将使我们更好地了解 成熟过程中化学感受器转导的机制。今年5月 导致治疗策略，可以改变化疗敏感性和 从而改善新生儿呼吸暂停和低通气的治疗，并 更老的话题。

Carotid body chemoreceptors are the primary sensory organs that cause ventilation to increase in response to a decrease in PaO2 or pHa. This responsiveness is weak at birth and increases during the first few weeks of life. Although the relationship between afferent sinus nerve activity and PaO2 or pHa is well characterized, the mechanisms of transduction and maturation are not understood. The glomus cell, in apposition to the afferent nerve ending, is the most likely site of transduction since chemosensitivity is ablated following glomus cell destruction. However, results of electrophysiologic studies on glomus cell response to hypoxia have been inconsistent between laboratories and preparations. For instance, opposing evidence exists that glomus cells are electrically excitable and unexcitable and that membrane ionic currents increase and decrease with hypoxia. In order to resolve these issues and understand the basis for chemosensitivity and its developmental change, we propose to employ patch clamp recording and optical measurements of glomus cells which are acutely isolated from rabbits. Our preliminary results have established our ability to harvest, patch-clamp and optically record from glomus cells of adults and newborns. We have demonstrated that hypoxic hypoxia and histotoxic hypoxia cause specific, but opposite, changes in a voltage-dependent outward current expressed in glomus cells, and the response to both agents is absent or reduced in the newborn glomus cell. The following general hypothesis is formulated: Chemotransduction of hypoxia is mediated by an O2 dependent change in a Ca++ binding protein. The following questions will be addressed: 1) What changes occur in sodium, potassium and calcium ionic membrane currents of adult glomus cells in response to hypoxia, increased H+ and decreased energy production? 2) How are intracellular Ca++ and pH regulated in glomus cells and do levels change with hypoxia? 3) What changes account for the maturational increase in carotid body hypoxia sensitivity? The anticipated results from this work will allow us to better understand the mechanisms of chemoreceptor transduction during maturation. This may lead to therapeutic strategies that can alter chemosensitivity and thereby improve treatment of apnea and hypoventilation in the neonate and older subject.