{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:20:16Z","timestamp":1772173216730,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1010607","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000}}],"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T00:00:00Z","timestamp":1671494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canada 150 Research Chair Program"},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2019-03916"],"award-info":[{"award-number":["RGPIN-2019-03916"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["Canada Graduate Scholarship - Doctoral"],"award-info":[{"award-number":["Canada Graduate Scholarship - Doctoral"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Maintaining normal potassium (K\n                    <jats:sup>+<\/jats:sup>\n                    ) concentrations in the extra- and intracellular fluid is critical for cell function. K\n                    <jats:sup>+<\/jats:sup>\n                    homeostasis is achieved by ensuring proper distribution between extra- and intracellular fluid compartments and by matching K\n                    <jats:sup>+<\/jats:sup>\n                    excretion with intake. The Na\n                    <jats:sup>+<\/jats:sup>\n                    -K\n                    <jats:sup>+<\/jats:sup>\n                    -ATPase pump facilitates K\n                    <jats:sup>+<\/jats:sup>\n                    uptake into the skeletal muscle, where most K\n                    <jats:sup>+<\/jats:sup>\n                    is stored. Na\n                    <jats:sup>+<\/jats:sup>\n                    -K\n                    <jats:sup>+<\/jats:sup>\n                    -ATPase activity is stimulated by insulin and aldosterone. The kidneys regulate long term K\n                    <jats:sup>+<\/jats:sup>\n                    homeostasis by controlling the amount of K\n                    <jats:sup>+<\/jats:sup>\n                    excreted through urine. Renal handling of K\n                    <jats:sup>+<\/jats:sup>\n                    is mediated by a number of regulatory mechanisms, including an aldosterone-mediated feedback control, in which high extracellular K\n                    <jats:sup>+<\/jats:sup>\n                    concentration stimulates aldosterone secretion, which enhances urine K\n                    <jats:sup>+<\/jats:sup>\n                    excretion, and a gastrointestinal feedforward control mechanism, in which dietary K\n                    <jats:sup>+<\/jats:sup>\n                    intake increases K\n                    <jats:sup>+<\/jats:sup>\n                    excretion. Recently, a muscle-kidney cross talk signal has been hypothesized, where the K\n                    <jats:sup>+<\/jats:sup>\n                    concentration in skeletal muscle cells directly affects urine K\n                    <jats:sup>+<\/jats:sup>\n                    excretion without changes in extracellular K\n                    <jats:sup>+<\/jats:sup>\n                    concentration. To understand how these mechanisms coordinate under different K\n                    <jats:sup>+<\/jats:sup>\n                    challenges, we have developed a compartmental model of whole-body K\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    -K\n                    <jats:sup>+<\/jats:sup>\n                    -ATPase K\n                    <jats:sup>+<\/jats:sup>\n                    uptake, and (iv) aldosterone stimulation of renal K\n                    <jats:sup>+<\/jats:sup>\n                    secretion. We used this model to investigate the impact of regulatory mechanisms on K\n                    <jats:sup>+<\/jats:sup>\n                    homeostasis. Model predictions showed how the regulatory mechanisms synthesize to ensure that the extra- and intracelluller fluid K\n                    <jats:sup>+<\/jats:sup>\n                    concentrations remain in normal range in times of K\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    concentration after a period of high K\n                    <jats:sup>+<\/jats:sup>\n                    loading or depletion.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1010607","type":"journal-article","created":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T13:38:52Z","timestamp":1671543532000},"page":"e1010607","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["A mathematical model of potassium homeostasis: Effect of feedforward and feedback controls"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4215-8004","authenticated-orcid":true,"given":"Melissa 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