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. 41 K was infused as KCl into rats consuming control or K + -deficient chow ( n = 4 each), 41 K-to- 39 K 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 41 K/ 39 K increased during 41 K infusion and decreased upon infusion cessation, without altering plasma total K + concentration ([K + ], i.e., 41 K + 39 K). 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, 41 K/ 39 K 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.