Sodium and Potassium Balance Depends on αENaC Expression in Connecting Tubule
Sodium and Potassium Balance Depends on αENaC Expression in Connecting Tubule
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DOI：
10.1681/asn.2009101077
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发表时间：
2010-11-01
影响因子：
13.6
通讯作者：
Hummler, Edith
中科院分区：
文献类型：
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作者：
Christensen, Birgitte Monster;Perrier, Romain;Hummler, Edith
上皮钠通道（ENaC）的α、β或γ亚基中的突变可下调ENaC活性并导致严重的盐丢失综合征，伴有高钾血症和代谢性酸中毒，在人类中称为假性醛固酮减少症1型。相反，集合管（CD）中α ENaC选择性失活的小鼠维持钠和钾平衡，提示晚期远曲小管（DCT 2）和/或连接小管（CNT）参与钠稳态。为了研究CNT中ENaC介导的钠吸收的相对重要性，我们使用Cre-lox技术产生表达CNT和CD的水通道蛋白2中缺乏α ENaC的小鼠CNT显示CCD中不存在α ENaC，CNT中α ENaC表达较弱。这些小鼠表现出显著较高的尿钠排泄，较低的尿渗透压，并且与对照小鼠相比尿量增加。此外，在遗传修饰的小鼠中，血清钠更低，钾水平更高。在饮食钠限制的情况下，这些小鼠经历了显著的体重减轻，尿钠排泄增加，和高钾血症血浆醛固酮水平在标准饮食和限钠饮食下均显著升高总之，CNT/CD中的α ENaC表达对于钠和钾的稳态至关重要，如果缺失，则会导致假性醛固酮减少症1型的体征和症状
Mutations in alpha, beta, or gamma subunits of the epithelial sodium channel (ENaC) can downregulate ENaC activity and cause a severe salt-losing syndrome with hyperkalemia and metabolic acidosis, designated pseudohypoaldosteronism type 1 in humans In contrast, mice with selective inactivation of alpha ENaC in the collecting duct (CD) maintain sodium and potassium balance, suggesting that the late distal convoluted tubule (DCT2) and/or the connecting tubule (CNT) participates in sodium homeostasis To investigate the relative importance of ENaC mediated sodium absorption in the CNT we used Cre-lox technology to generate mice lacking alpha ENaC in the aquaporin 2 expressing CNT and CD Western blot analysis of microdissected cortical CD (CCD) and CNT revealed absence of alpha ENaC in the CCD and weak alpha ENaC expression in the CNT These mice exhibited a significantly higher urinary sodium excretion, a lower urine osmolality, and an increased urine volume compared with control mice Furthermore, serum sodium was lower and potassium levels were higher in the genetically modified mice With dietary sodium restriction these mice experienced significant weight loss, increased urinary sodium excretion, and hyperkalemia Plasma aldosterone levels were significantly elevated under both standard and sodium restricted diets In summary, alpha ENaC expression within the CNT/CD is crucial for sodium and potassium homeostasis and causes signs and symptoms of pseudohypoaldosteronism type 1 if missing