Collecting duct-specific gene inactivation of alphaENaC in the mouse kidney does not impair sodium and potassium balance.
Collecting duct-specific gene inactivation of alphaENaC in the mouse kidney does not impair sodium and potassium balance.
复制标题
小鼠肾脏中 alphaENaC 收集管特异性基因失活不会损害钠和钾平衡。
DOI：
10.1172/jci16956
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Rossier,BernardC
中科院分区：
文献类型：
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作者：
Rubera,Isabelle;Loffing,Johannes;Palmer,LawrenceG;Frindt,Gustavo;Fowler-Jaeger,Nicole;Sauter,Daniel;Carroll,Tom;McMahon,Andrew;Hummler,Edith;Rossier,BernardC
醛固酮通过调节对醛固酮敏感的远端肾单位上皮钠通道(ENaC)的活动来控制肾脏最终的钠重吸收和钾的分泌。ASDN由远曲小管的最后部分(晚期DCT)、连接小管(CNT)和集合管(CD)(即皮质CD[Ccd]和髓质Cd[MCD])组成。已有的研究表明，控制细胞内钠离子的转运是实现钠钾平衡的关键。我们已经通过灭活CD中ENaC的α亚单位来检验这一假设，但在DCT晚期和CNT中保持ENaC的表达不变。在盐限制或醛固酮输注条件下，CCD主细胞的全细胞电压钳未检测到ENaC活性，而对照仔猪出现了较大的阿米洛利敏感电流。这些动物存活得很好，能够保持钠和钾的平衡，即使受到盐限制、缺水或钾负荷的挑战。我们的结论是，ENaC在CD中的表达不是实现小鼠钠钾平衡的先决条件。这强调了更多近端肾单位节段(晚期DCT/CNT)对实现钠钾平衡的重要性。
Aldosterone controls the final sodium reabsorption and potassium secretion in the kidney by regulating the activity of the epithelial sodium channel (ENaC) in the aldosterone-sensitive distal nephron (ASDN). ASDN consists of the last portion of the distal convoluted tubule (late DCT), the connecting tubule (CNT), and the collecting duct (CD) (i.e., the cortical CD [CCD] and the medullary CD [MCD]). It has been proposed that the control of sodium transport in the CCD is essential for achieving sodium and potassium balance. We have tested this hypothesis by inactivating the α subunit of ENaC in the CD but leaving ENaC expression in the late DCT and CNT intact. Under salt restriction or under aldosterone infusion, whole-cell voltage clamp of principal cells of CCD showed no detectable ENaC activity, whereas large amiloride-sensitive currents were observed in control littermates. The animals survive well and are able to maintain sodium and potassium balance, even when challenged by salt restriction, water deprivation, or potassium loading. We conclude that the expression of ENaC in the CD is not a prerequisite for achieving sodium and potassium balance in mice. This stresses the importance of more proximal nephron segments (late DCT/CNT) to achieve sodium and potassium balance.