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Potassium Modulates Electrolyte Balance and Blood Pressure through Effects on Distal Cell Voltage and Chloride
Open accessAbstract
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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“Additionally, WNK1 interacts with chloride ions (Cl−) to alter its conformation, facilitating the capture of SGK1 (Piala et al., 2014; Terker et al., 2015). This conformational change promotes the interaction between Mammalian Target of Rapamycin Complex 2 (mTORC2) and SGK1 and enhances the phosphorylation of SGK1 while simultaneously inhibiting the kinase activity of WNK1.”
From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Terker et al., 2015
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Self-citationUrinary Sodium and Potassium Excretion, Mortality, and Cardiovascular Events
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“Recently, in two studies of individuals from around the world, low K+ (LK) intake was strongly associated with both higher blood pressure C and cardiovascular death (Mente et al., 2014; O’Donnell et al., 2014).”
Association of Urinary Sodium and Potassium Excretion with Blood Pressure
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Chloride sensing by WNK1 involves inhibition of autophosphorylation
Piala, A. T., Moon, T. M., Akella, R., He, H., Cobb, M. H., & Goldsmith, E. J. (2014) · Science Signaling · doi:10.1126/scisignal.2005050 · Cited by 418
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Metadata
- 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
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 21
- Issue
- 1
- Pages
- 39-50
- ISSN
- 1550-4131 (ISSN-L)
- 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
- 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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