Regulation of renal Na transporters in response to dietary K.
Regulation of renal Na transporters in response to dietary K.
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DOI：
10.1152/ajprenal.00117.2018
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发表时间：
2018-10
期刊：
影响因子：
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通讯作者：
Lei Yang;Shuhua Xu;Xiaoyun Guo;S. Uchida;A. Weinstein;Tong Wang;L. Palmer
中科院分区：
文献类型：
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作者：
Lei Yang;Shuhua Xu;Xiaoyun Guo;S. Uchida;A. Weinstein;Tong Wang;L. Palmer
增加膳食钾摄入量1周的小鼠肾脏中的Na转运蛋白的表达的变化进行了测定。上皮Na通道（ENaC）上调，全长和裂解形式的α-ENaC和裂解的γ-ENaC表达增强。与此同时，NaCl协同转运蛋白NCC及其磷酸化形式的量分别减少了约50%和约80%。磷酸化形式的Na-K-2Cl协同转运蛋白NKCC 2的表达也下降，尽管总体蛋白质含量增加。男性（80%）比女性（40%）的影响更大。这意味着较少的Na+与Cl-一起在Henle袢和远曲小管的粗升支中被重吸收，而更多的Na+在醛固酮敏感的远端肾单位中被重吸收以交换分泌的K+。近端小管Na/H交换器NHE 3的丰度降低约40%，雄性和雌性动物的影响相似。时程研究表明，NCC和NHE 3蛋白在高钾饮食7天内逐渐下降。编码这些蛋白质的mRNA的表达增加，这意味着蛋白质水平降低是由于合成速率降低或降解速率增加。用数学模型评估了NHE 3、NKCC 2和NCC在促进K+排泄方面的变化的潜在重要性。模拟表明，NHE 3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稳态中起重要作用。
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.