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高钾饮食激活肾远曲小管肾外髓钾通道

李雪^1,*, 李鹏辉¹, 肖宇¹, 赵堃¹, 赵红晔¹, 卢长柱¹, 齐晓娟¹, 谷瑞民²

¹齐齐哈尔医学院生理学教研室，齐齐哈尔 161000；²哈尔滨医科大学药学院，哈尔滨 150081

摘要

肾外髓钾通道(renal outer medullary potassium channel, ROMK)是肾脏重要的排钾通道，经ROMK通道分泌的K+是尿钾大部分或全部的来源。既往在肾小管离子转运机制调控研究中，学者多将ROMK通道的研究靶点集中于髓袢和集合管，对肾远曲小管末段(late distal convoluted tubule, DCT2) ROMK通道参与机体K+排泄的研究较少。本研究旨在应用单通道及全细胞膜片钳技术，在肾DCT2顶端膜记录ROMK通道电流并观察高钾饮食对该通道活性的影响。结果显示，在肾DCT2顶端膜可记录到一种电导为39 pS的小电导通道电流，且该电流可被ROMK通道特异性阻断药抑制。与正常钾饮食组相比，高钾饮食能够显著增加肾DCT2顶端膜ROMK通道电流出现的概率，增强该通道活性(P < 0.01)。Western blot结果显示，高钾饮食能够显著上调肾脏ROMK通道及上皮钠通道(epithelial sodium channel, ENaC)的蛋白表达，下调肾脏钠-氯同向转运体(Na+-Cl− cotransporter, NCC)的蛋白表达，且高钾饮食小鼠尿钾排泄量显著增加。上述结果提示，高钾饮食可能通过上调肾脏ROMK通道蛋白的表达激活肾DCT2顶端膜ROMK通道，促进尿钾排泄。

关键词： 肾外髓钾通道; 远曲小管末段; 高钾饮食; 上皮钠通道; 膜片钳技术

Activation of renal outer medullary potassium channel in the renal distal convoluted tubule by high potassium diet 

LI Xue^1,*, LI Peng-Hui¹, XIAO Yu¹, ZHAO Kun¹, ZHAO Hong-Ye¹, LU Chang-Zhu¹, QI Xiao-Juan¹, GU Rui-Min²

¹Department of Physiology, Qiqihar Medical College, Qiqihar 161000, China；²Department of Pharmacology, Harbin Medical University, Harbin 150081, China

Abstract

Renal outer medullary potassium (ROMK) channel is an important K+ excretion channel in the body, and K+ secreted by the ROMK channels is most or all source of urinary potassium. Previous studies focused on the ROMK channels of thick ascending limb (TAL) and collecting duct (CD), while there were few studies on the involvement of ROMK channels of the late distal convoluted tubule (DCT2) in K+ excretion. The purpose of the present study was mainly to record the ROMK channels current in renal DCT2 and observe the effect of high potassium diet on the ROMK channels by using single channel and whole-cell patch-clamp techniques. The results showed that a small conductance channel current with a conductance of 39 pS could be recorded in the apical membrane of renal DCT2, and it could be blocked by Tertiapin-Q (TPNQ), a ROMK channel inhibitor. The high potassium diet significantly increased the probability of ROMK channel current occurrence in the apical membrane of renal DCT2, and enhanced the activity of ROMK channel, compared to normal potassium diet (P < 0.01). Western blot results also demonstrated that the high potassium diet significantly up-regulated the protein expression levels of ROMK channels and epithelial sodium channel (ENaC), and down-regulated the protein expression level of Na+-Cl− cotransporter (NCC). Moreover, the high potassium diet significantly increased urinary potassium excretion. These results suggest that the high potassium diet may activate the ROMK channels in the apical membrane of renal DCT2 and increase the urinary potassium excretion by up-regulating the expression of renal ROMK channels.

Key words: renal outer medullary potassium channel; late distal convoluted tubule; high potassium diet; epithelial sodium channel; patch-clamp technique

收稿日期：　　录用日期：

通讯作者：李雪　　E-mail: lixue_0720@163.com

DOI: 10.13294/j.aps.2023.0006

引用本文：

李雪, 李鹏辉, 肖宇, 赵堃, 赵红晔, 卢长柱, 齐晓娟, 谷瑞民. 高钾饮食激活肾远曲小管肾外髓钾通道[J]. 生理学报 2023; 75 (2): 188-196.

LI Xue, LI Peng-Hui, XIAO Yu, ZHAO Kun, ZHAO Hong-Ye, LU Chang-Zhu, QI Xiao-Juan, GU Rui-Min. Activation of renal outer medullary potassium channel in the renal distal convoluted tubule by high potassium diet . Acta Physiol Sin 2023; 75 (2): 188-196 (in Chinese with English abstract).