Feedback inhibition of ENaC during acute sodium loading in vivo.
Feedback inhibition of ENaC during acute sodium loading in vivo.
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DOI：
10.1152/ajprenal.00596.2012
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发表时间：
2013-01
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影响因子：
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通讯作者：
Ankit B. Patel;G. Frindt;L. Palmer
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文献类型：
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作者：
Ankit B. Patel;G. Frindt;L. Palmer
上皮Na(+)通道(ENaC)受到钠摄入量的严格调节，以维持全身钠稳态。此外，ENaC 受到细胞内高水平 Na(+) [Na(+)](i) 的抑制，可能是为了防止细胞 Na(+) 过载和肿胀。然而，尚不清楚该调节是否与体内相关。我们在此表明，在大鼠中，即使通过输注激素使血浆醛固酮水平保持较高水平，急性（4小时）口服钠负荷也会降低皮质集合管（CCD）中的全细胞阿米洛利敏感电流（I（Na））。伴随着全肾裂解 α-ENaC（2.6 倍）、总 β-ENaC（1.7 倍）和裂解 γ-ENaC（6.2 倍）的减少。此外，使用原位生物素化测量细胞表面 β- 和 γ-ENaC 表达。细胞表面核心糖基化（2.2 倍）和成熟糖基化（4.9 倍）β-ENaC 和裂解 γ-ENaC（4.7 倍）减少。其他顶端钠转运蛋白没有显着变化。为了研究 Na(+) 进入和可能的 [Na(+)](i) 增加对 ENaC 的作用，在钠负荷之前和期间给动物输注阿米洛利。阻断Na(+)进入并不能抑制重盐化对I(Na)的影响。然而，阿米洛利确实阻止了 ENaC 表达的降低，这是氢氯噻嗪给药无法模仿的效果。 Na(+) 的进入和可能的 [Na(+)](i) 可以调节 ENaC 表达，但不能完全解释急性钠负荷期间 I(Na) 的独立于醛固酮的下降。
The epithelial Na(+) channel (ENaC) is tightly regulated by sodium intake to maintain whole body sodium homeostasis. In addition, ENaC is inhibited by high levels of intracellular Na(+) [Na(+)](i), presumably to prevent cell Na(+) overload and swelling. However, it is not clear if this regulation is relevant in vivo. We show here that in rats, an acute (4 h) oral sodium load decreases whole-cell amiloride-sensitive currents (I(Na)) in the cortical collecting duct (CCD) even when plasma aldosterone levels are maintained high by infusing the hormone. This was accompanied by decreases in whole-kidney cleaved α-ENaC (2.6 fold), total β-ENaC (1.7 fold), and cleaved γ-ENaC (6.2 fold). In addition, cell-surface β- and γ-ENaC expression was measured using in situ biotinylation. There was a decrease in cell-surface core-glycosylated (2.2 fold) and maturely glycosylated (4.9 fold) β-ENaC and cleaved γ-ENaC (4.7 fold). There were no significant changes for other apical sodium transporters. To investigate the role of increases in Na(+) entry and presumably [Na(+)](i) on ENaC, animals were infused with amiloride prior to and during sodium loading. Blocking Na(+) entry did not inhibit the effect of resalting on I(Na). However, amiloride did prevent decreases in ENaC expression, an effect that was not mimicked by hydrochlorothiazide administration. Na(+) entry and presumably [Na(+)](i) can regulate ENaC expression but does not fully account for the aldosterone-independent decrease in I(Na) during an acute sodium load.