Intracellular chloride: a regulator of transepithelial transport in the distal nephron.

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.

• Publication year

  2019

• Venue

  Current opinion in nephrology and hypertension

• Publication date

  2019-07-01

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1097/MNH.0000000000000502PMID 30865168PMCID PMC6684285
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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