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, < 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 ( < 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.