Potassium intake modulates the thiazide-sensitive sodium-chloride cotransporter (NCC) activity via the Kir4.1 potassium channel.
Potassium intake modulates the thiazide-sensitive sodium-chloride cotransporter (NCC) activity via the Kir4.1 potassium channel.
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钾摄入量通过 Kir4.1 钾通道调节噻嗪类敏感的氯化钠协同转运蛋白 (NCC) 活性。
DOI：
10.1016/j.kint.2017.10.023
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发表时间：
2018-04
影响因子：
19.6
通讯作者：
Ellison DH
中科院分区：
文献类型：
--
作者：
Wang MX;Cuevas CA;Su XT;Wu P;Gao ZX;Lin DH;McCormick JA;Yang CL;Wang WH;Ellison DH
远曲小管（DCT）中的Kir4.1在感知血浆K+和调节噻嗪类药物敏感的Na-Cl共转运体（NCC）中起关键作用。本研究的目的是测试饮食中K+摄入是否调节Kir4.1，以及这是否在K+饮食对NCC的影响中起重要作用。高K+ (HK)摄入抑制了Kcnj10flox/flox（对照或WT）小鼠DCT基底外侧40ps K+通道（Kir4.1/5.1异聚体），降低了基底外侧K+电导，并使DCT膜去极化。相反，低K+ (LK)摄入激活Kir4.1，增加K+电流，并使DCT膜超极化。然而，在诱导型肾特异性Kir4.1敲除（KS-Kir4.1 KO）小鼠中，饮食K+摄入量对DCT基底外侧K+电导和膜电位的影响完全不存在。此外，hk的摄入减少了NCC的表达，而lk的摄入增加了NCC的表达丰度，只有在WT小鼠中，而在KS-Kir4.1 KO小鼠中没有。肾清除率研究表明，氢氯噻嗪（HCTZ）在WT小鼠中引起的尿钠，LK增加，HK减少。Kir4.1的破坏显著增加了基础尿Na+排泄，但消除了HCTZ的利钠作用。最后，K+限制加重了KS-Kir4.1 KO小鼠的低钾血症和代谢性碱中毒，HK饮食只能部分纠正。综上所述，Kir4.1在膳食K+摄入量对NCC活性和K+稳态的影响中发挥了重要作用。
Kir4.1 in the distal convoluted tubule (DCT) plays a key role in sensing plasma K+ and in modulating the thiazide-sensitive Na-Cl cotransporter (NCC). The aim of current study was to test whether dietary K+ intake modulates Kir4.1, and whether this is essential for mediating the effect of K+ diet on NCC. High K+ (HK) intake inhibited the basolateral 40 pS K+ channel (a Kir4.1/5.1 heterotetramer) in the DCT, decreased basolateral K+ conductance, and depolarized the DCT membrane in Kcnj10flox/flox (control or WT) mice. In contrast, low K+ (LK) intake activated Kir4.1, increased K+ currents, and hyperpolarized the DCT membrane. These effects of dietary K+ intake on the basolateral K+ conductance and membrane potential in the DCT were, however, completely absent in inducible kidney-specific Kir4.1 knockout (KS-Kir4.1 KO) mice. Furthermore, HK-intake decreased whereas LK-intake increases the abundance of NCC expression only in WT but not in KS-Kir4.1 KO mice. Renal clearance studies demonstrated that LK augmented, while HK diminished, hydrochlorothiazide (HCTZ)-induced natriuresis in WT mice. Disruption of Kir4.1 significantly increased basal urinary Na+ excretion but it abolished the natriuretic effect of HCTZ. Finally, hypokalemia and metabolic alkalosis in KS-Kir4.1 KO mice were exacerbated by K+ restriction and only partially corrected by HK diet. We conclude that Kir4.1 plays an essential role in mediating the effect of dietary K+ intake on NCC activity and K+ homeostasis.
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影响因子：
30.8
作者：
Lalioti, Maria D.;Zhang, Junhui;Lifton, Richard P.
通讯作者：
Lifton, Richard P.
影响因子：
5.5
作者：
Lourdel, S;Paulais, M;Teulon, J
通讯作者：
Teulon, J
影响因子：
4.8
作者：
Ponce-Coria, Jose;Markadieu, Nicolas;Delpire, Eric
通讯作者：
Delpire, Eric
影响因子：
64.8
作者：
Boyden, Lynn M.;Choi, Murim;Choate, Keith A.;Nelson-Williams, Carol J.;Farhi, Anita;Toka, Hakan R.;Tikhonova, Irina R.;Bjornson, Robert;Mane, Shrikant M.;Colussi, Giacomo;Lebel, Marcel;Gordon, Richard D.;Semmekrot, Ben A.;Poujol, Alain;Valimaki, Matti J.;De Ferrari, Maria E.;Sanjad, Sami A.;Gutkin, Michael;Karet, Fiona E.;Tucci, Joseph R.;Stockigt, Jim R.;Keppler-Noreuil, Kim M.;Porter, Craig C.;Anand, Sudhir K.;Whiteford, Margo L.;Davis, Ira D.;Dewar, Stephanie B.;Bettinelli, Alberto;Fadrowski, Jeffrey J.;Belsha, Craig W.;Hunley, Tracy E.;Nelson, Raoul D.;Trachtman, Howard;Cole, Trevor R. P.;Pinsk, Maury;Bockenhauer, Detlef;Shenoy, Mohan;Vaidyanathan, Priya;Foreman, John W.;Rasoulpour, Majid;Thameem, Farook;Al-Shahrouri, Hania Z.;Radhakrishnan, Jai;Gharavi, Ali G.;Goilav, Beatrice;Lifton, Richard P.
通讯作者：
Lifton, Richard P.
影响因子：
19.6
作者：
Chiga, Motoko;Rai, Tatemitsu;Uchida, Shinichi
通讯作者：
Uchida, Shinichi