Potassium modulates electrolyte balance and blood pressure through effects on distal cell voltage and chloride

Andrew S. Terker, Chong Zhang, James A. McCormick, Rebecca A. Lazelle, Chengbiao Zhang, Nicholas P. Meermeier, Dominic A. Siler, Hae J. Park, Yi Fu, David M. Cohen, Alan M. Weinstein, Wen Hui Wang, Chao Ling Yang, David H. Ellison

Research output: Contribution to journalArticle

182 Scopus citations

Abstract

Dietary potassium deficiency, common in modern diets, raises blood pressure and enhances salt sensitivity. Potassium homeostasis requires a molecular switch in the distal convoluted tubule (DCT), which fails in familial hyperkalemic hypertension (pseudohypoaldosteronism type 2), activating the thiazide-sensitive NaCl cotransporter, NCC. Here, we show that dietary potassium deficiency activates NCC, even in the setting of high salt intake, thereby causing sodium retention and a rise in blood pressure. The effect is dependent on plasma potassium, which modulates DCT cell membrane voltage and, in turn, intracellular chloride. Low intracellular chloride stimulates WNK kinases to activate NCC, limiting potassium losses, even at the expense of increased blood pressure. These data show that DCT cells, like adrenal cells, sense potassium via membrane voltage. In the DCT, hyperpolarization activates NCC via WNK kinases, whereas in the adrenal gland, it inhibits aldosterone secretion. These effects work in concert to maintain potassium homeostasis.

Original languageEnglish (US)
Pages (from-to)39-50
Number of pages12
JournalCell Metabolism
Volume21
Issue number1
DOIs
StatePublished - Jan 6 2015

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Potassium modulates electrolyte balance and blood pressure through effects on distal cell voltage and chloride'. Together they form a unique fingerprint.

  • Cite this

    Terker, A. S., Zhang, C., McCormick, J. A., Lazelle, R. A., Zhang, C., Meermeier, N. P., Siler, D. A., Park, H. J., Fu, Y., Cohen, D. M., Weinstein, A. M., Wang, W. H., Yang, C. L., & Ellison, D. H. (2015). Potassium modulates electrolyte balance and blood pressure through effects on distal cell voltage and chloride. Cell Metabolism, 21(1), 39-50. https://doi.org/10.1016/j.cmet.2014.12.006