Estimating in vivo potassium distribution and fluxes with stable potassium isotopes

Jang H. Youn, Young Taek Oh, Stefania Gili, Alicia A. McDonough, John Higgins

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Extracellular potassium (K+) homeostasis is achieved by a concerted effort of multiple organs and tissues. A limitation in studies of K+ homeostasis is inadequate techniques to quantify K+ fluxes into and out of organs and tissues in vivo. The goal of the present study was to test the feasibility of a novel approach to estimate K+ distribution and fluxes in vivo using stable K+ isotopes.41K was infused as KCl into rats consuming control or K+-deficient chow (n = 4 each), 41K-to-39K ratios in plasma and red blood cells (RBCs) were measured by inductively coupled plasma mass spectrometry, and results were subjected to compartmental modeling. The plasma 41K/39K increased during 41K infusion and decreased upon infusion cessation, without altering plasma total K+ concentration ([K+], i.e., 41K + 39K). The time course of changes was analyzed with a two-compartmental model of K+ distribution and elimination. Model parameters, representing transport into and out of the intracellular pool and renal excretion, were identified in each rat, accurately predicting decreased renal K+ excretion in rats fed K+-deficient vs. control diet (P < 0.05). To estimate rate constants of K+ transport into and out of RBCs, 41K/39K were subjected to a simple model, indicating no effects of the K+-deficient diet. The findings support the feasibility of the novel stable isotope approach to quantify K+ fluxes in vivo and sets a foundation for experimental protocols using more complex models to identify heterogeneous intracellular K+ pools and to answer questions pertaining to K+ homeostatic mechanisms in vivo.

Original languageEnglish (US)
Pages (from-to)C410-C420
JournalAmerican Journal of Physiology - Cell Physiology
Issue number3
StatePublished - Mar 2022

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology


  • compartmental modeling
  • isotope ratio analysis
  • potassium homeostasis
  • potassium transport
  • renal excretion


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