Kinetic Modeling of In Vivo K⁺ Distribution and Fluxes with Stable K⁺ Isotopes: Effects of Dietary K⁺ Restriction

Maintaining extracellular potassium (K⁺) within narrow limits, critical for membrane potential and excitability, is accomplished through the internal redistribution of K⁺ between extracellular fluid (ECF) and intracellular fluid (ICF) in concert with the regulation of renal K⁺ output to balance K⁺ intake. Here we present evidence from high-precision analyses of stable K⁺ isotopes in rats maintained on a control diet that the tissues and organs involved in the internal redistribution of K⁺ differ in their speed of K⁺ exchange with ECF and can be grouped into those that exchange K⁺ with ECF either rapidly or more slowly ("fast" and "slow" pools). After 10 days of K⁺ restriction, a compartmental analysis indicates that the sizes of the ICF K⁺ pools decreased but that this decrease in ICF K⁺ pools was not homogeneous, rather occurring only in the slow pool (15% decrease, p < 0.01), representing skeletal muscles, not in the fast pool. Furthermore, we find that the dietary K⁺ restriction is associated with a decline in the rate constants for K⁺ effluxes from both the "fast" and "slow" ICF pools (p < 0.05 for both). These results suggest that changes in unidentified transport pathways responsible for K⁺ efflux from ICF to ECF play an important role in buffering the internal redistribution of K⁺ between ICF and ECF during K⁺ restriction. Thus, the present study introduces novel stable isotope approaches to separately characterize heterogenous ICF K⁺ pools in vivo and assess K⁺ uptake by individual tissues, methods that provide key new tools to elucidate K⁺ homeostatic mechanisms in vivo.