1. Potassium modulates electrolyte balance and blood pressure through effects on distal cell voltage and chloride.
- Author
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Terker AS, Zhang C, McCormick JA, Lazelle RA, Zhang C, Meermeier NP, Siler DA, Park HJ, Fu Y, Cohen DM, Weinstein AM, Wang WH, Yang CL, and Ellison DH
- Subjects
- Animals, Cell Line, Chlorides metabolism, Humans, Kidney Tubules, Distal metabolism, Membrane Potentials drug effects, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Minor Histocompatibility Antigens, Potassium blood, Potassium metabolism, Potassium Channels, Inwardly Rectifying genetics, Potassium Channels, Inwardly Rectifying metabolism, Protein Serine-Threonine Kinases genetics, Protein Serine-Threonine Kinases metabolism, Pseudohypoaldosteronism metabolism, Pseudohypoaldosteronism pathology, Sodium Chloride, Dietary pharmacology, Solute Carrier Family 12, Member 3 deficiency, Solute Carrier Family 12, Member 3 genetics, Solute Carrier Family 12, Member 3 metabolism, WNK Lysine-Deficient Protein Kinase 1, Blood Pressure drug effects, Electrolytes urine, Potassium, Dietary pharmacology
- 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., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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