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Abstract：
Kir4.1 in the distal convoluted tubule plays a key role in sensing plasma potassium and in modulating the thiazide-sensitive sodium-chloride cotransporter (NCC). Here we tested whether dietary potassium intake modulates Kir4.1 and whether this is essential for mediating the effect of potassium diet on NCC. High potassium intake inhibited the basolateral 40 pS potassium channel (a Kir4.1/5.1 heterotetramer) in the distal convoluted tubule, decreased basolateral potassium conductance, and depolarized the distal convoluted tubule membrane in Kcnj10flox/flox mice, herein referred to as control mice. In contrast, low potassium intake activated Kir4.1, increased potassium currents, and hyperpolarized the distal convoluted tubule membrane. These effects of dietary potassium intake on the basolateral potassium conductance and membrane potential in the distal convoluted tubule were completely absent in inducible kidney-specific Kir4.1 knockout mice. Furthermore, high potassium intake decreased, whereas low potassium intake increased the abundance of NCC expression only in the control but not in kidney-specific Kir4.1 knockout mice. Renal clearance studies demonstrated that low potassium augmented, while high potassium diminished, hydrochlorothiazide-induced natriuresis in control mice. Disruption of Kir4.1 significantly increased basal urinary sodium excretion but it abolished the natriuretic effect of hydrochlorothiazide. Finally, hypokalemia and metabolic alkalosis in kidney-specific Kir4.1 knockout mice were exacerbated by potassium restriction and only partially corrected by a high-potassium diet. Thus, Kir4.1 plays an essential role in mediating the effect of dietary potassium intake on NCC activity and potassium homeostasis.
摘要：
远曲小管中的Kir4.1在感知血浆钾和调节噻嗪敏感的氯化钠协同转运蛋白（NCC）中起关键作用。在这里，我们测试了膳食钾摄入量是否调节Kir4.1，以及这对于介导钾饮食对NCC的影响是否至关重要。高钾摄入抑制了远曲小管的基底外侧40pS钾通道（Kir4.1/5.1异四聚体），基底外侧钾电导降低，并使Kcnj10flox/flox小鼠的远曲小管膜去极化，本文称为对照小鼠。相比之下,低钾摄入量激活Kir4.1，增加钾电流，并使远曲小管膜超极化。在可诱导的肾脏特异性Kir4.1敲除小鼠中，饮食钾摄入量对远曲小管基底外侧钾电导和膜电位的影响完全不存在。此外，高钾摄入量减少，而低钾摄入量仅在对照组中增加了NCC表达的丰度，而在肾脏特异性Kir4.1敲除小鼠中没有增加。肾脏清除率研究表明，低钾增加，虽然高钾减少，氢氯噻嗪诱导的对照小鼠利钠。Kir4.1的破坏显着增加了基础尿钠排泄，但消除了氢氯噻嗪的利钠作用。最后,在肾脏特异性Kir4.1基因敲除小鼠中,低钾血症和代谢性碱中毒因限制钾而加重,高钾饮食仅部分纠正.因此，Kir4.1在调节膳食钾摄入量对NCC活性和钾稳态的影响中起着至关重要的作用。
