Estimating in vivo potassium distribution and fluxes with stable potassium isotopes

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.