DEVELOPMENT OF LUNG EPITHELIAL CELL ION TRANSPORT

在胎儿期，呼吸上皮细胞通过呼吸道分泌产生肺液。 涉及活性氯（Cl-）分泌的过程。 出生后远端 肺上皮细胞吸收钠（Na+）和水。成功 出生时胎儿肺液的吸收对于有效地 出生后肺气体交换 出生时吸收液体， 出生后保持相对干燥的空气空间需要 从出生前的Cl-分泌到出生后的Na+吸收。 的 拟议工作的总体目标是澄清机制， 这一转变的规律。 这项工作将确定和确定 离子运动的不同途径的相对重要性 在发育过程中穿过远端肺上皮，并检查 与出生和肺发育相关的各种激素在 调节离子运输。 具体目标是衡量 新鲜离体和培养的远端肺的Na+和Cl-转运 从胎兔、新生兔和成年兔分离的上皮细胞; 确定选定的离子转运抑制剂的作用和潜在的 调节激素对Na+和Cl-转运这些细胞;并使 胎儿肺腔液体运动的相关测定 羊 这些研究涉及协调使用3种互补的 评估远端肺上皮细胞离子转运的实验模型 细胞和这些细胞的离子转运变化的重要性， 出生时肺液的流动。 它们涉及测量 新鲜分离和培养的细胞的放射性标记离子摄取， 生物电特性（跨上皮电特性）的测量 电位差、短路电流和电阻） 细胞单层，并测量肺腔液体分泌， 在活胎动物中的吸收。 拟议项目将包括 实验旨在帮助从一个人的信息 另一个实验模型。 这些互补模型允许 在3个不同组织水平上评价离子转运 （细胞、上皮和器官水平）。 这 综合方法是获得全面理解的关键 离子运输的发育变化之间的关系 远端肺上皮细胞和液体从空气中的去除 出生时的肺 这种理解可能具有重要意义 关于围产期肺液体平衡和疾病状态， 肺泡液体平衡异常起作用。

During fetal life the respiratory epithelium produces lung liquid by a process involving active chloride (Cl-) secretion. After birth distal lung epithelial cells absorb sodium (Na+) and water. The successful absorption of fetal lung liquid during birth is essential for effective postnatal pulmonary gas exchange. Absorption of liquid during birth and maintanence of relatively dry airspaces after birth requires a transition from prenatal Cl- secretion to postnatal Na+ absorption. The overal objective of the proposed work is to clarify the mechanisms and the regulation of this transition. The work will identify and determine thc relative importance of different pathways for the movement of ions across the distal lung epithelium during development and examine the role of various hormones relevant to birth and lung development in regulating ion transport. The specific aims are to measure changes in Na+ and Cl- transport by freshly isolated and cultured distal lung epithelial cells isolated from fetal, newborn and adult rabbits; to determine the effects of selected ion transport inhibitors and potential regulatory hormones on Na+ and Cl- transport by these cells; and to make correlative measurements of lung luminal liquid movement in living fetal sheep. These studies involve the coordinated use of 3 complementary experimental models to assess ion transport by distal lung epithelial cells and the importance of changes in ion transport by these cells to the movement of lung liquid during birth. They involve measurement of radiolabelled ion uptake by freshly isolated and cultured cells, measurement of bioelectrical properties (transepithelial electrical potential difference, short-circuit current, and resistance) of cultured cell monolayers, and measurement of lung luminal liquid secretion and absorption in living fetal animals. The proposed project will include experiments designed to assist in relating information from one experimental model to another. These complementary models allow for the evaluation of ion transport at 3 different levels of tissue organization (cellular, epithelial and organ levels) during development. This integrated approach is essential to attaining a thorough understanding of the relationship between developmental changes in ion transport by distal lung epithelium and the removal of liquid from the airspaces of the lung at birth. Such understanding may have important implications concerning perinatal lung liquid balance and disease states where abnormal alveolar fluid balance plays a role.