Intracellular chloride: a regulator of transepithelial transport in the distal nephron.
Intracellular chloride: a regulator of transepithelial transport in the distal nephron.
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DOI：
10.1097/mnh.0000000000000502
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发表时间：
2019-07
影响因子：
3.2
通讯作者：
Aylin R. Rodan
中科院分区：
文献类型：
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作者：
Aylin R. Rodan
综述的目的：本综述着重于细胞内氯离子在调节远曲小管（DCT）跨上皮离子转运中的作用，以响应血浆钾稳态的扰动。低钾饮食增加DCT中氯化钠协同转运蛋白（NCC）的磷酸化和活性，反之亦然，影响下游醛固酮敏感性远端肾单位的钠依赖性钾分泌。在细胞中，NCC磷酸化通过降低细胞内氯化物而增加，经由无赖氨酸（WNK）-SPAK/OSR 1（Ste 20相关脯氨酸/富含丙氨酸的激酶/氧化应激反应）激酶级联的氯化物敏感性的激活。体内研究表明，低钾饮食可激活肾脏中的通路。一个可能的机制是降低DCT细胞内氯响应低钾，因为平行的基底外侧钾和氯通道。最近的研究支持这些通道在NCC对不同钾的响应中的作用。在果蝇肾小管和小鼠中研究氯不敏感的WNK突变体的研究进一步支持了氯在调节WNK活性和跨上皮离子转运中的作用。警告，替代品，和未来的方向也进行了讨论。通过WNK激酶的氯传感提供了一种机制，允许细胞外钾与NCC磷酸化和活性偶联以维持钾稳态。
PURPOSE OF REVIEW This review focuses on the role of intracellular chloride in regulating transepithelial ion transport in the distal convoluted tubule (DCT) in response to perturbations in plasma potassium homeostasis. RECENT FINDINGS Low dietary potassium increases the phosphorylation and activity of the sodium chloride cotransporter (NCC) in the DCT, and vice versa, affecting sodium-dependent potassium secretion in the downstream aldosterone-sensitive distal nephron. In cells, NCC phosphorylation is increased by lowering of intracellular chloride, via activation of the chloride-sensitive with no lysine (WNK)-SPAK/OSR1 (Ste20-related proline/alanine-rich kinase/oxidative stress response) kinase cascade. In-vivo studies have demonstrated pathway activation in the kidney in response to low dietary potassium. A possible mechanism is lowering of DCT intracellular chloride in response to low potassium because of parallel basolateral potassium and chloride channels. Recent studies support a role for these channels in the response of NCC to varying potassium. Studies examining chloride-insensitive WNK mutants, in the Drosophila renal tubule and in the mouse, lend further support to a role for chloride in regulating WNK activity and transepithelial ion transport. Caveats, alternatives, and future directions are also discussed. SUMMARY Chloride sensing by WNK kinase provides a mechanism to allow coupling of extracellular potassium with NCC phosphorylation and activity to maintain potassium homeostasis.