Cited by 457Potassium and Related DisordersIon Transport and Channel RegulationSodium Intake and Health

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Potassium Modulates Electrolyte Balance and Blood Pressure through Effects on Distal Cell Voltage and Chloride

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Terker, Andrew S., Zhang, Chong, McCormick, James A., Lazelle, Rebecca A., Zhang, Chengbiao, Meermeier, Nicholas P., Siler, Dominic A., Park, Hae J., Fu, Yi, Cohen, David M., Weinstein, Alan M., Wang, Wen-Hui, Yang, Chao-Ling, Ellison, David H.·2015·Cell Metabolism

DOI 10.1016/j.cmet.2014.12.006PMC PMC4332769

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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.

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Authors: 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.
Affiliations: Oregon Health & Science University (US)
New York Medical College (US)
Corresponding author: Ellison, David H.
ORCID: Terker, Andrew S.
Zhang, Chong
McCormick, James A.
Siler, Dominic A.
Park, Hae J.
Fu, Yi
Cohen, David M.
Weinstein, Alan M.
Ellison, David H.
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2015-01
Volume: 21
Issue: 1
Pages: 39-50
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2014.12.006
PMC: PMC4332769
OpenAlex: W1970486445
Cited by: 457
References: 44
Citations by year: 2026: 35 · 2025: 23 · 2024: 38 · 2023: 40 · 2022: 53 · 2021: 38 · 2020: 38 · 2019: 42 · 2018: 41 · 2017: 47 · 2016: 38 · 2015: 24
FWCI: 39.60
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 370 d)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: U.S. Department of Veterans Affairs (I01BX002228)
National Institute of General Medical Sciences (T32GM071338)
National Institute of Diabetes and Digestive and Kidney Diseases (DK-51496, DK 54983, DK098141, R56DK054983, DK-29857, R01DK029857, R01DK054983, T32DK067864, R01DK051496, R01DK098141)
National Center for Research Resources (S10RR023432)
Topics: Health Sciences › Medicine › Nephrology › Potassium and Related Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
Health Sciences › Nursing › Nutrition and Dietetics › Sodium Intake and Health
Keywords: distal convoluted tubule, thiazide-sensitive NaCl cotransporter, NCC, WNK kinases, membrane hyperpolarization, intracellular chloride, potassium homeostasis, blood pressure, salt sensitivity, sodium retention, aldosterone secretion, electrolyte balance
MeSH terms: WNK Lysine-Deficient Protein Kinase 1, Kcnj10 Channel, Animals, Blood Pressure, Cell Line, Chlorides, Electrolytes, Humans, Kidney Tubules, Distal, Membrane Potentials, Mice, Inbred BALB C, Mice, Inbred C57BL, Potassium, Pseudohypoaldosteronism, Minor Histocompatibility Antigens, Protein Serine-Threonine Kinases, Potassium, Dietary, Sodium Chloride, Dietary, Mice, Knockout, Potassium Channels, Inwardly Rectifying, Mice, Solute Carrier Family 12, Member 3

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Potassium Modulates Electrolyte Balance and Blood Pressure through Effects on Distal Cell Voltage and Chloride

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