肾远曲小管（DCT）重吸收约5-10%的Na+，是醛固酮及噻嗪类利尿剂作用的重要部位; Kir 4.1/ 5.1钾通道是DCT管周膜最主要的功能性钾通道，其功能失活或降低导致管腔膜NCC活性降低；而NCC活性增强导致高血压及电解质紊乱。PGF2α灌注可以升高血压，其受体FP敲除呈低血压表现。DCT是PGF2α作用的靶小管，预实验研究发现，PGF2α能显著激活Kir 4.1/ 5.1钾通道，我们推测，PGF2α通过某信号转导通路激活DCT管周膜Kir4.1/5.1钾通道，同时（或）促进该通道的表达，进而激活NCC，最终促进NaCl的重吸收而参与高血压的形成。本项目将采用单通道和全细胞膜片钳记录及分子生物学技术相结合的方法研究PGF2α对肾远曲小管Kir4.1/5.1钾通道的作用并探讨其调控机制。本项目的完成将完善PGF2α参与高血压形成的机制，并为临床高血压及电解质紊乱的防治提供新思路。

The distal convoluted tubule (DCT) can reabsorb 5-10% of the total filtered load of Na+ in the kidney, plays an important role in urine concentration and dilution. As the target of thiazide diuretic and aldosterone, DCT makes a great contribution to salt and water balance. The Kir 4.1/ 5.1 channels, as the main functional K channel in the basolateral membrane, participate in generating the cell membrane potential and recycle K+ across the membrane, which is the driving force for the reabsorption of Cl- and plays a key role in maintaining Na-K-ATPase and Na+- Cl- cotransporter (NCC) activity. Either Kir 4.1/5.1 channels loss function or with low function decrease the activity of NCC. Prostaglandin F2α (PGF2α) infusion increases blood pressure (BP) whereas BP is reduced in FP-/- mice; and FP receptor is highly dectected in DCT. We have found that 500nM PGF2α increased the Kir 4.1/5.1 channel activity in the pre-experiment. Therefore, we plan to use single-channel recording, whole-cell patch-clamp and molecular biology technique to explore the effect and modulation mechanism of PGF2α on the basolateral Kir 4.1/5.1 channels in the DCT1. The aim of the project is to demonstrate the hypothesis that PGF2α may stimulate the Kir 4.1/5.1 channels on the basolateral membrane of DCT1 through activating some signal transduction and (or) up-regulating the expression of the Kir 4.1/5.1 channels, thereby increasing the activity of NCC and increasing the reabsorption of NaCl, which may be involved in the development of hypertension induced by PGF2α. This study would provide a new idea for the prevention and treatment of hypertension and electrolyte imbalances.