A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls
Bibliographic record
Abstract
Abstract Maintaining normal potassium (K + ) concentrations in the extra- and intracellular fluid is critical for cell function. K + homeostasis is achieved by ensuring proper distribution between extra- and intracellular fluid compartments and by matching K + excretion with intake. The Na + -K + -ATPase pump facilitates K + uptake into the skeletal muscle, where most K + is stored. Na + -K + -ATPase activity is stimulated by insulin and aldosterone. The kidneys regulate long term K + regulation by controlling the amount of K + excreted through urine. Renal handling of K + is mediated by a number of regulatory mechanisms, including an aldosterone-mediated feedback control, in which high extracellular K + concentration stimulates aldosterone secretion which enhances urine K + excretion, and a gastrointestinal feedforward control mechanism, in which dietary K + intake increases K + excretion. Recently, a muscle-kidney cross talk signal has been hypothesized, where the K + concentration in skeletal muscle cells directly affects urine K + excretion without changes in extracellular K + concentration. To understand how these mechanisms coordinate under different K + challenges, we have developed a compartmental model of whole-body K + regulation. The model represents the intra- and extracellular fluid compartments in a human (male) as well as a detailed kidney compartment. We included (i) the gastrointestinal feedforward control mechanism, (ii) the effect of insulin and (iii) aldosterone on Na + -K + -ATPase K + uptake, and (iv) aldosterone stimulation of renal K + secretion. We used this model to investigate the impact of regulatory mechanisms on K + homeostasis. Model predictions showed how the regulatory mechanisms synthesize to ensure that the extra- and intracelluller fluid K + concentrations remain in normal range in times of K + loading and fasting. Additionally, we predict that without the hypothesized muscle-kidney cross talk signal, the model was unable to predict a return to normal extracellular K + concentration after a period of high K + loading or depletion. Author summary Potassium (K + ) homeostasis is crucial for normal cell function. Dysregulation of K + can have dangerous consequences and is a common side effect of pathologies, medications, or changes in hormone levels. Due to its complexities, how the body maintains extra- and intracellular K + concentrations each day is not fully understood. Of particular interest is capturing how regulatory mechanisms synthesize to be able to keep extracellullar K + concentration within a tight range of 3.5-5.0 mEq/L. There are a multitude of physiological processes involved in K + balance, making its study well suited for investigation using mathematical modeling. In this study, we developed a compartment model of extra- and intracellular K + regulation including the various regulatory mechanisms and a detailed kidney model. The significance of our research is to quantify the effect of individual regulatory mechanisms on K + regulation as well as predict the potential impact of a hypothesized signal: muscle-kidney cross talk.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".