Maxi-K channels contribute to urinary potassium excretion in the ROMK- deficient mouse model of Type II Bartter's syndrome and in adaptation to a high-K diet
Maxi-K channels contribute to urinary potassium excretion in the ROMK- deficient mouse model of Type II Bartter's syndrome and in adaptation to a high-K diet
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DOI：
10.1038/sj.ki.5000388
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发表时间：
2006-07-01
影响因子：
19.6
通讯作者：
Malnic, G.
中科院分区：
文献类型：
--
作者：
Bailey, M. A.;Cantone, A.;Malnic, G.
II型Bartter综合征是由ROMK通道（Kir1.1; Kcnj1）突变引起的遗传性低钾血症性肾盐消耗疾病，该通道介导Henle's袢（TAL）厚升肢体的钾循环以及远端小管和皮质集管（CCT）的钾分泌。II型Bartter新生儿是短暂性高钾血症，与远曲小管和CCT中钾分泌的ROMK通道功能丧失一致。然而，由于未知机制介导的肾钾排泄增加，这些婴儿迅速发展为持续性低钾血症。在此，我们采用自由流动微穿刺和固定微灌注的方法来探讨romk缺乏的II型Bartter小鼠肾钾消耗的机制。我们发现在romk缺陷小鼠中，Henle环中的钾吸收减少，并且可以解释肾钾损失的很大一部分。此外，我们发现，尽管ROMK功能丧失，但iberiotoxin （IBTX）敏感的、血流刺激的最大钾通道在末梢小管中持续分泌钾。ibtx敏感的钾分泌也在高钾适应野生型小鼠中增加。因此，II型Bartter患者的肾钾消耗是由于TAL重吸收减少和末梢小管的max-K通道分泌钾。
Type II Bartter's syndrome is a hereditary hypokalemic renal salt-wasting disorder caused by mutations in the ROMK channel (Kir1.1; Kcnj1), mediating potassium recycling in the thick ascending limb of Henle's loop (TAL) and potassium secretion in the distal tubule and cortical collecting duct (CCT). Newborns with Type II Bartter are transiently hyperkalemic, consistent with loss of ROMK channel function in potassium secretion in distal convoluted tubule and CCT. Yet, these infants rapidly develop persistent hypokalemia owing to increased renal potassium excretion mediated by unknown mechanisms. Here, we used free-flow micropuncture and stationary microperfusion of the late distal tubule to explore the mechanism of renal potassium wasting in the Romk-deficient, Type II Bartter's mouse. We show that potassium absorption in the loop of Henle is reduced in Romk-deficient mice and can account for a significant fraction of renal potassium loss. In addition, we show that iberiotoxin (IBTX)-sensitive, flow-stimulated maxi-K channels account for sustained potassium secretion in the late distal tubule, despite loss of ROMK function. IBTX-sensitive potassium secretion is also increased in high-potassium-adapted wild-type mice. Thus, renal potassium wasting in Type II Bartter is due to both reduced reabsorption in the TAL and K secretion by max-K channels in the late distal tubule.