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Cited by 61Potassium and Related DisordersIon Transport and Channel RegulationIon channel regulation and function

Potassium homeostasis: sensors, mediators, and targets

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McDonough, Alicia A., Fenton, Robert A.·2022·Pflügers Archiv - European Journal of Physiology
DOI 10.1007/s00424-022-02718-3PMC PMC10163916
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Abstract

Transmembrane potassium (K) gradients are key determinants of membrane potential that can modulate action potentials, control muscle contractility, and influence ion channel and transporter activity. Daily K intake is normally equal to the amount of K in the entire extracellular fluid (ECF) creating a critical challenge - how to maintain ECF [K] and membrane potential in a narrow range during feast and famine. Adaptations to maintain ECF [K] include sensing the K intake, sensing ECF [K] vs. desired set-point and activating mediators that regulate K distribution between ECF and ICF, and regulate renal K excretion. In this focused review, we discuss the basis of these adaptions, including (1) potential mechanisms for rapid feedforward signaling to kidney and muscle after a meal (before a rise in ECF [K]), (2) how skeletal muscles sense and respond to changes in ECF [K], (3) effects of K on aldosterone biosynthesis, and (4) how the kidney responds to changes in ECF [K] to modify K excretion. The concepts of sexual dimorphisms in renal K handling adaptation are introduced, and the molecular mechanisms that can account for the benefits of a K-rich diet to maintain cardiovascular health are discussed. Although the big picture of K homeostasis is becoming more clear, we also highlight significant pieces of the puzzle that remain to be solved, including knowledge gaps in our understanding of initiating signals, sensors and their connection to homeostatic adjustments of ECF [K].

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Crossref · 10.1007/s00424-022-02718-3

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  • In humans, normal extracellular K+ concentration is about 3.5-5.0 mEq/L.

    “In humans, normal extracellullar K+ concentration is about 3.5–5.0 mEq/L; intracellular K+ concentration is about 120–140 mEq/L [1, 3].”

    From A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls (2022) · cites this paper as [1]

    The Introduction gives extracellular K+ concentration in mammals as 3.8–5 mM, which applies to humans and is equivalent to mEq/L for K+. It supports the approximate range but gives a lower bound of 3.8, not 3.5. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Aldosterone increases K+ secretion into distal segments of nephrons and increases cellular K+ uptake via Na+-K+-ATPase pump stimulation.

    “ALD impacts K+ regulation by increasing K+ secretion into the distal segments of the nephrons, as well as increasing cellular K+ uptake via Na+-K+-ATPase pump stimulation [1, 13].”

    From A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls (2022) · cites this paper as [1]

    The kidney-handling section (page unavailable) explains that aldosterone affects K+ secretion in the distal nephron. The aldosterone-biosynthesis section (page unavailable) considers a possible role in cellular K+ uptake but says it is difficult to distinguish that effect from K+ excretion; it does not establish that aldosterone stimulates cellular Na+-K+-ATPase to increase uptake. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Recommended daily K+ intake is 120 mEq, about 70% more than the extracellular K+ pool.

    “A second challenge is that K+ has the highest ratio of daily intake to extracellular pool size of all the major electrolytes: recommended daily intake of K+ is 120 mEq [1], about 70% more than the extracellular K+ pool.”

    From A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls (2022) · cites this paper as [1]

    The Introduction gives daily K+ intake as 70–120 mEq and the extracellular K+ pool as approximately 70 mEq; 120 mEq is therefore about 70% greater than the pool. It does not identify 120 mEq as the recommended daily intake, which is the specific point attached to the citation. Page numbers are unavailable in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • In humans, normal intracellular K+ concentration is about 120-140 mEq/L.

    “In humans, normal extracellullar K+ concentration is about 3.5–5.0 mEq/L; intracellular K+ concentration is about 120–140 mEq/L [1, 3].”

    From A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls (2022) · cites this paper as [1]

  • The extracellular K+ pool is much smaller than the intracellular K+ pool (70 compared to 3,500 mEq).

    “That could produce a substantial perturbation in extracellular K+ concentration, given that the extracellular pool is much smaller than the intracellular pool (70 compared to 3,500 mEq [1, 3]).”

    From A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls (2022) · cites this paper as [1]

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Cited by

Sorted by citations

Authors
McDonough, A. A., & Fenton, R. A.
Affiliations
  • University of Southern California (US)
  • Aarhus University (DK)
Corresponding author
McDonough, Alicia A.
ORCID
Venue
Pflügers Archiv - European Journal of Physiology
Publisher
Springer Science and Business Media LLC
Published
2022-06-21
Volume
474
Issue
8
Pages
853-867
ISSN
  • 0031-6768 (ISSN-L)
  • 1432-2013
DOI
10.1007/s00424-022-02718-3
PMC
PMC10163916
OpenAlex
W4283213847
Cited by
61
References
10
Citations by year
2026: 18 · 2025: 8 · 2024: 17 · 2023: 12 · 2022: 6
FWCI
1.86
Type
journal article
Language
en
Open access
Licence
Locations
  • Pflügers Archiv - European Journal of Physiology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK123780, DK132613)
  • Fondation Leducq (17CVD05)
  • Novo Nordisk Fonden (NNF21OC0067647, NNF17OC0029724, NNF19OC0058439)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Potassium and Related Disorders
  • 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
Keywords
potassium homeostasis, membrane potential, potassium intake, renal potassium excretion, aldosterone biosynthesis, potassium-rich diet, cardiovascular health, potassium transporters, ion channels
MeSH terms
Sodium-Potassium-Exchanging ATPase, Homeostasis, Kidney, Potassium, Muscle, Skeletal, Extracellular Fluid

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