Na-K-Cl Cotransporter Molecular Expression & Function During Development

Na-K-Cl 协同转运蛋白分子表达

• 批准号: 6262820
• 负责人: Lynn M Iwamoto
• 金额: $ 39万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6262820
• 关键词: chloride ion; clinical research; cooperative study; developmental genetics; erythrocytes; erythroid stem cell; essential hypertension; furosemide; gene expression; gestational age; guinea pigs; human fetus tissue; human subject; immunocytochemistry; ion transport; membrane transport proteins; muscle relaxation; pharmacogenetics; posttranslational modifications; potassium ion; respiratory muscles; sodium ion; tissue /cell culture

The Na-K-2Cl (sodium-potassium-2-chloride) cotransporter is an electroneutral membrane protein that plays several important roles in cellular physiology. Recent data suggest that the Na-K-2CI cotransporter may play a role in airway smooth muscle relaxation. However, molecular identification of this co-transporter protein airway smooth muscle has not been confirmed. More fundamentally, this cotransporter protein in airway smooth muscle has not been confirmed. More fundamentally, this cotransporter regulates salt and water secretion across epithelial cells and maintenance and regulation of cell volume and ion gradients in epithelial and non-epithelial cells (e.g., erythrocytes). The erythrocyte cotransporter appears important because the level of activity in adults with essential hypertension has been correlated with the diuretic and natriuretic responses to furosemide, suggesting genetic variation in cotransporter regulation. Characterization of the Na-K-2Cl cotransporter in human erythroid progenitor cells and neonatal erythrocytes would provide information about developmental changes in the cotransporter expression and function. The present proposal focuses on the Na-K-2CL cotransporter in the neonatal guinea pig and human fetal airways and in the human neonatal erythrocyte and its precursor, the erythroid progenitor cell. The following hypotheses will be tested: 1) the Na-K-2Cl cotransporter is expressed in airway smooth muscle; 2) changes in erythrocyte cotransporter expression and activity occur with maturation; and 3) the regulation of the human Na-K-2Cl cotransporter is similar to that found in animal paradigms. Results of this project will further our understanding of the importance of the Na-K-2Cl cotransporter by providing evidence for its role in loop diuretic mediated airway smooth muscle relaxation. Also, characterization of the Na-K-2Cl cotransporter in the human erythrocyte with the study of its function and changes in maturation may provide new insights into the developmental regulation of this cotransporter as well as in understanding kidney function and the development of essential hypertension.

Na-K-2Cl（钠-氯钾）共转运体是一种电中性膜蛋白，在细胞生理中起着重要作用。最近的研究表明Na-K-2CI共转运蛋白可能在气道平滑肌松弛中起作用。然而，这种气道平滑肌共转运蛋白的分子鉴定尚未得到证实。更根本的是，这种共转运蛋白在气道平滑肌中的作用尚未得到证实。更根本的是，这种共转运体调节上皮细胞的盐和水分泌，以及上皮细胞和非上皮细胞（如红细胞）中细胞体积和离子梯度的维持和调节。红细胞共转运蛋白之所以显得重要，是因为成人原发性高血压患者的活性水平与对速尿的利尿和利钠反应相关，这表明共转运蛋白调控存在遗传变异。研究Na-K-2Cl共转运蛋白在人红细胞祖细胞和新生儿红细胞中的表达和功能，有助于了解其在发育过程中的变化。目前的建议集中在新生儿豚鼠和人胎儿气道和人新生儿红细胞及其前体红祖细胞中的Na-K-2CL共转运体。本文将检验以下假设：1)Na-K-2Cl共转运蛋白在气道平滑肌中表达；2)红细胞共转运蛋白的表达和活性随成熟发生变化；3)人类Na-K-2Cl共转运体的调控与动物范式相似。该项目的结果将通过为Na-K-2Cl共转运蛋白在利尿剂介导的气道平滑肌松弛中的作用提供证据，进一步了解Na-K-2Cl共转运蛋白的重要性。此外，研究Na-K-2Cl在人红细胞中的共转运体及其功能和成熟过程中的变化，可能为研究Na-K-2Cl的发育调控以及了解肾功能和原发性高血压的发生提供新的见解。