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Cited by 49Ion Transport and Channel RegulationIon channel regulation and functionPotassium and Related Disorders

ENaC and ROMK channels in the connecting tubule regulate renal K+ secretion

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Yang, Lei, Xu, Yuanyuan, Gravotta, Diego, Frindt, Gustavo, Weinstein, Alan M., Palmer, Lawrence G.·2021·Journal of General Physiology
DOI 10.1085/jgp.202112902PMC PMC8217949
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Abstract

We measured the activities of epithelial Na channels (ENaC) and ROMK channels in the distal nephron of the mouse kidney and assessed their role in the process of K+ secretion under different physiological conditions. Under basal dietary conditions (0.5% K), ENaC activity, measured as amiloride-sensitive currents, was high in cells at the distal end of the distal convoluted tubule (DCT) and proximal end of the connecting tubule (CNT), a region we call the early CNT (CNTe). In more distal parts of the CNT (aldosterone-sensitive portion [CNTas]), these currents were minimal. This functional difference correlated with alterations in the intracellular location of ENaC, which was at or near the apical membrane in CNTe and more cytoplasmic in the CNTas. ROMK activity, measured as TPNQ-sensitive currents, was substantial in both segments. A mathematical model of the rat nephron suggested that K+ secretion by the CNTe predicted from these currents provides much of the urinary K+ required for K balance on this diet. In animals fed a K-deficient diet (0.1% K), both ENaC and ROMK currents in the CNTe decreased by ∼50%, predicting a 50% decline in K+ secretion. Enhanced reabsorption by a separate mechanism is required to avoid excessive urinary K+ losses. In animals fed a diet supplemented with 3% K, ENaC currents increased modestly in the CNTe but strongly in the CNTas, while ROMK currents tripled in both segments. The enhanced secretion of K+ by the CNTe and the recruitment of secretion by the CNTas account for the additional transport required for K balance. Therefore, adaptation to increased K+ intake involves the extension of robust K+ secretion to more distal parts of the nephron.

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  • The distal tubule's capacity to reabsorb K+ is limited to up to 3% of filtered K+ in male rats.

    “However, the distal tubule’s capacity to reabsorb K+ is limited (up to 3% of filtered K+ in male rats), meaning that in times of drastically low K+ intake, it is up to the downstream collecting duct to conserve K+ via reabsorption [7, 8].”

    From A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls (2022) · cites this paper as [8]

    The Results (Low-K diet; page unavailable) and Discussion (Physiological significance; page unavailable) say that K+ secretion persists during dietary K restriction, requiring downstream reabsorption to conserve K+. They do not give a distal-tubule reabsorptive limit of 3% of filtered K+ in male rats, or establish that reabsorption must occur specifically in the collecting duct rather than elsewhere in the distal nephron. (LLM, conf=0.84)

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  • The rate of K+ secretion is regulated by dietary K+ intake, intracellular K+ concentration, Na+ uptake into the cells, urine flow rate, and hormones such as aldosterone and angiotensin II.

    “The rate of K+ secretion is regulated by dietary K+ intake, intracellular K+ concentration, Na+ uptake into the cells, urine flow rate, and hormones such as ALD and angiotensin II [7, 8].”

    From A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls (2022) · cites this paper as [8]

    The Introduction (page not provided) links Na+ entry to the rate of K+ secretion and identifies aldosterone as a major determinant of renal K+ excretion. The Discussion, under Physiological significance, reports changes in secretion with dietary K+ intake, while the Introduction notes a possible role for high urine flow. The cited passages do not establish intracellular K+ concentration or angiotensin II as regulators. (LLM, conf=0.87)

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Authors
Yang, L., Xu, Y., Gravotta, D., Frindt, G., Weinstein, A. M., & Palmer, L. G.
Affiliations
Weill Cornell Medicine (US)
Corresponding author
Palmer, Lawrence G.
ORCID
Venue
Journal of General Physiology
Publisher
Rockefeller University Press
Published
2021-06-18
Volume
153
Issue
8
ISSN
  • 0022-1295 (ISSN-L)
  • 1540-7748
DOI
10.1085/jgp.202112902
PMC
PMC8217949
OpenAlex
W3168270741
Cited by
49
References
42
Citations by year
2026: 9 · 2025: 5 · 2024: 13 · 2023: 7 · 2022: 12 · 2021: 3
FWCI
2.75
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of General Physiology (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
National Institutes of Health (R01-DK111380, R01-DK29857)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Potassium and Related Disorders
Keywords
epithelial sodium channel, ROMK channel, potassium secretion, connecting tubule, distal convoluted tubule, amiloride-sensitive current
MeSH terms
Animals, Kidney Tubules, Distal, Nephrons, Sodium, Potassium Channels, Inwardly Rectifying, Mice, Rats, Epithelial Sodium Channels

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