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

Na-K-2Cl(钠-钾-2-氯)共转运蛋白是一种电子中和膜蛋白，在细胞生理中发挥着重要作用。最近的数据表明，Na-K-2CI共转运体可能在气道平滑肌松弛中起作用。然而，这种共转运蛋白的分子鉴定尚未得到证实。更根本的是，这种共转运蛋白在呼吸道平滑肌中的作用尚未得到证实。更根本的是，这种共转运蛋白调节上皮细胞间的盐和水的分泌，以及维持和调节上皮细胞和非上皮细胞(如红细胞)中的细胞体积和离子梯度。红细胞共转运体似乎很重要，因为高血压成人的活动水平与利尿剂和利尿剂对速尿的反应相关，这表明共转运体调节的遗传变异。对人红系祖细胞和新生儿红细胞中Na-K-2Cl共转运体的鉴定将为该共转运体的表达和功能的发育变化提供信息。本研究主要针对新生豚鼠和人胎儿呼吸道内Na-K-2CL共转运体以及人新生儿红细胞及其前体红系祖细胞的Na-K-2CL共转运体进行研究。将检验以下假设：1)Na-K-2Cl共转运体在气道平滑肌中表达；2)红细胞共转运体的表达和活性随成熟而发生变化；3)人的Na-K-2Cl共转运体的调节类似于动物模型中发现的。本项目的结果将进一步加深我们对Na-K-2Cl共转运体的重要性的理解，为其在环状利尿剂介导的气道平滑肌松弛中的作用提供证据。此外，对人红细胞Na-K-2Cl共转运体的特性及其功能和成熟度变化的研究，可能为了解该共转运体的发育规律以及了解肾功能和高血压的发生发展提供新的见解。

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.