Deletion of Kir5.1 Impairs Renal Ability to Excrete Potassium during Increased Dietary Potassium Intake.
Deletion of Kir5.1 Impairs Renal Ability to Excrete Potassium during Increased Dietary Potassium Intake.
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DOI：
10.1681/asn.2019010025
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发表时间：
2019-06
期刊：
影响因子：
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通讯作者：
Peng Wu;Zhong-Xiuzi Gao;Dan-dan Zhang;X. Su;Wen‐Hui Wang;Daohong Lin
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作者：
Peng Wu;Zhong-Xiuzi Gao;Dan-dan Zhang;X. Su;Wen‐Hui Wang;Daohong Lin
远曲小管（DCT）的基底外侧钾通道（包括内向整流钾通道Kir4.1/Kir5.1异源四聚体）在介导膳食钾摄入对噻嗪敏感性NaCl协同转运蛋白（NCC）的影响中起关键作用。Kir5.1（由Kcnj 16编码）在介导膳食钾摄入对NCC和肾钾排泄的影响中的作用尚不清楚。方法我们采用电生理学、肾清除率和免疫印迹法研究Kir5.1基因敲除（Kcnj 16-/-）和野生型（Kcnj 16 +/+）小鼠DCT和NCC中Kir4.1的表达，这些小鼠分别喂食正常、高钾或低钾饮食。结果在野生型和基因敲除小鼠的DCT基底外侧膜上分别检测到40 pS和20 pS的钾通道。与野生型相比，正常钾饮食喂养的Kcnj 16-/-小鼠具有更高的基底侧钾电导，更负的DCT膜电位，更高的磷酸化NCC（pNCC）和总NCC（tNCC）表达，并增强噻嗪诱导的尿钠排泄。高钾和低钾饮食均不影响Kcnj 16-/-小鼠基底外侧DCT的钾电导和膜电位。虽然高钾降低和低钾增加野生型小鼠pNCC和tNCC的表达，但这些作用在Kcnj 16-/-小鼠中不存在。高钾摄入抑制和低摄入增加噻嗪诱导的尿钠排泄在野生型，但不是在Kcnj 16-/-小鼠。与野生型相比，正常钾摄入量的Kcnj 16-/-小鼠的血浆钾水平略低，但随着长时间高钾摄入量的增加，高钾血症更为严重，限钾期间低钾血症更为严重。结论Kir5.1是膳食钾对NCC的影响和维持钾稳态所必需的。
BACKGROUND The basolateral potassium channel in the distal convoluted tubule (DCT), comprising the inwardly rectifying potassium channel Kir4.1/Kir5.1 heterotetramer, plays a key role in mediating the effect of dietary potassium intake on the thiazide-sensitive NaCl cotransporter (NCC). The role of Kir5.1 (encoded by Kcnj16) in mediating effects of dietary potassium intake on the NCC and renal potassium excretion is unknown. METHODS We used electrophysiology, renal clearance, and immunoblotting to study Kir4.1 in the DCT and NCC in Kir5.1 knockout (Kcnj16-/- ) and wild-type (Kcnj16+/+ ) mice fed with normal, high, or low potassium diets. RESULTS We detected a 40-pS and 20-pS potassium channel in the basolateral membrane of the DCT in wild-type and knockout mice, respectively. Compared with wild-type, Kcnj16-/- mice fed a normal potassium diet had higher basolateral potassium conductance, a more negative DCT membrane potential, higher expression of phosphorylated NCC (pNCC) and total NCC (tNCC), and augmented thiazide-induced natriuresis. Neither high- nor low-potassium diets affected the basolateral DCT's potassium conductance and membrane potential in Kcnj16-/- mice. Although high potassium reduced and low potassium increased the expression of pNCC and tNCC in wild-type mice, these effects were absent in Kcnj16-/- mice. High potassium intake inhibited and low intake augmented thiazide-induced natriuresis in wild-type but not in Kcnj16-/- mice. Compared with wild-type, Kcnj16-/- mice with normal potassium intake had slightly lower plasma potassium but were more hyperkalemic with prolonged high potassium intake and more hypokalemic during potassium restriction. CONCLUSIONS Kir5.1 is essential for dietary potassium's effect on NCC and for maintaining potassium homeostasis.