STIMULUS SECRETION COUPLING IN CAROTID BODY GLOMUS CELLS

呼吸系统和心血管系统的主要传感器 低氧是颈动脉小体的化学感受器，可增加其活性。 以应对PaO2或PHA的下降。对这些刺激的敏感度是 出生时虚弱，在出生后的头一到两周内增长。低氧和 酸性很可能是由血管球体细胞、分泌细胞 与传入神经末梢相对。他们的作用是必不可少的 化学转导，因为分离后失去了化疗敏感性 神经末梢的球状细胞。最新的膜片钳记录 分离的血管球瘤细胞显示一种K电流，该电流被低氧抑制。 这种抑制被认为在 缺氧的转导级联，导致去极化，钙内流 和增强型发射器释放。然而，我们的初步问题是 这一机制的有效性，因为缺氧往往不能改变细胞膜 血管球体细胞电流，原位和钾阻滞剂，尽管 极大地影响细胞电流，可能不会阻断神经或 器官的分泌反应。 拟议的实验解决了关于以下两个基本问题 转导过程。首先，球体细胞的身份是什么？ 低氧时释放的分泌物是什么？这个问题是由 检查：i)钠、钾和钙通道在启动过程中的重要性 球体细胞分泌，II)钙离子与细胞的关系 分泌和iii)核苷酸和磷酸化酶的调节作用 关于分泌活动。其次，在水平上或在 对分泌物的敏感性可解释儿童发育能力的增加 球瘤细胞刺激/分泌偶联？ 计划中的实验将采用一种新的、独特的化学感受器模型。 它允许同时进行单纤维神经记录，并且 球菌儿茶酚胺释放的测定或膜片钳记录 手机。膜片钳数据用于评估囊泡融合事件 通过高分辨率的膜电容监测。儿茶酚胺 使用碳纤维、Nafion涂层微电极测量分泌物 结合扫描或安培伏安法。 这项工作的预期结果将使我们更好地了解 血管球体细胞缺氧和酸度转导的机制及其机制 对这些生理反应的敏感度逐渐增强的基础 刺激物。这可能会导致治疗策略的改变 从而改善对呼吸暂停和呼吸暂停的治疗 新生儿和年长受试者的换气不足。

The primary sensor of the respiratory and cardiovascular systems for hypoxia are the carotid body chemoreceptors which increase their activity in response to a decrease in PaO2 or PHa. Sensitivity to these stimuli are weak at birth and increase over the first week or two of life. Hypoxia and acidity are likely transduced by glomus cells, secretory cells in apposition to the afferent nerve endings. Their role is essential to chemotransduction because chemosensitivity is lost following separation of the glomus cell from the nerve endings. Recent patch clamp recordings of isolated glomus cells revealed a K+ current which is inhibited by hypoxia. This inhibition is hypothesized to play an essential role in the transduction cascade of hypoxia, leading to depolarization, calcium influx and enhanced transmitter release. However, our preliminary question the validity of this mechanism because hypoxia often fails to alter membrane currents of glomus cells, in situ, and K+ blocking agents, although greatly effecting the cellular currents, may not block the nerve or secretory response of the organ. The proposed experiments address two basic questions regarding the transduction process. Firstly, what is the identity of glomus cell secretogues and which are liberated during hypoxia? This is addressed by examining: i) the importance of Na+, K+ and Ca+2 channels in initiating glomus cells secretion, ii) the relationship between Ca+2i and cell secretion and iii) the modulatory role of nucleotides and phosphorylases on secretory activity. Secondly, what change occurs in the level of or sensitivity to secretogues to account for the developmental increase in glomus cell stimulus/secretion coupling? The proposed experiments will employ a new and unique chemoreceptor model which allows for simultaneous single-fiber nerve recordings and either measurement of catecholamine release or patch-clamp recording of glomus cell. Patch-clamp data is used for assessment of vesicular fusion events by high-resolution monitoring of membrane capacitance. Catecholamine secretion is measured using carbon-fiber, Nafion coated microelectrodes combined with scanning or amperometric voltammetry. The anticipated results from this work will allow us to better understand the mechanisms of glomus cell hypoxia and acidity transduction and the basis for the maturational increase in sensitivity to these physiologic stimuli. This may lead to therapeutic strategies that can alter chemosensitivity and thereby improve treatment of apnea and hypoventilation in the neonate and older subject.