Department of Physiology and Biophysics, Weill Medical College of Cornell University , New York, New York.
Department of Cellular and Molecular Physiology, Yale University , New Haven, Connecticut.
Am J Physiol Renal Physiol. 2018 Oct 1;315(4):F1032-F1041. doi: 10.1152/ajprenal.00117.2018. Epub 2018 Jun 20.
Changes in the expression of Na transport proteins were measured in the kidneys of mice with increased dietary K intake for 1 wk. The epithelial Na channel (ENaC) was upregulated, with enhanced expression of full-length and cleaved forms of α-ENaC and cleaved γ-ENaC. At the same time, the amount of the NaCl cotransporter NCC and its phosphorylated form decreased by ~50% and ~80%, respectively. The expression of the phosphorylated form of the Na-K-2Cl cotransporter NKCC2 also decreased, despite an increase in overall protein content. The effect was stronger in males (80%) than in females (40%). This implies that less Na is reabsorbed in the thick ascending limb of Henle's loop and distal convoluted tubule along with Cl, whereas more is reabsorbed in the aldosterone-sensitive distal nephron in exchange for secreted K. The abundance of the proximal tubule Na/H exchanger NHE3 decreased by ~40%, with similar effects in males and females. Time-course studies indicated that NCC and NHE3 proteins decreased progressively over 7 days on a high-K diet. Expression of mRNA encoding these proteins increased, implying that the decreased protein levels resulted from decreased rates of synthesis or increased rates of degradation. The potential importance of changes in NHE3, NKCC2, and NCC in promoting K excretion was assessed with a mathematical model. Simulations indicated that decreased NHE3 produced the largest effect. Regulation of proximal tubule Na transport may play a significant role in achieving K homeostasis.
研究人员在高钾饮食喂养 1 周的小鼠肾脏中测量了钠转运蛋白表达的变化。上皮钠通道（ENaC）上调，全长和裂解形式的α-ENaC 和裂解γ-ENaC 的表达增强。与此同时，NaCl 协同转运蛋白 NCC 的量及其磷酸化形式分别减少了约 50%和 80%。尽管 Na-K-2Cl 协同转运蛋白 NKCC2 的总蛋白含量增加，但磷酸化形式的表达也减少了。这种影响在雄性（80%）中比雌性（40%）更强。这意味着在醛固酮敏感的远端肾单位中，与 Cl 一起，在 Henle 袢升支粗段和远端卷曲小管中再吸收的 Na 减少，而在远端肾单位中再吸收的 Na 增加，以交换分泌的 K。近端小管 Na/H 交换蛋白 NHE3 的丰度降低了约 40%，雄性和雌性的影响相似。时程研究表明，在高钾饮食下，NCC 和 NHE3 蛋白在 7 天内逐渐减少。这些蛋白编码的 mRNA 表达增加，这意味着蛋白水平的降低是由于合成率降低或降解率增加所致。通过数学模型评估了 NHE3、NKCC2 和 NCC 变化在促进 K 排泄方面的潜在重要性。模拟表明，NHE3 的减少产生的影响最大。近端小管 Na 转运的调节可能在实现 K 体内平衡中起重要作用。
