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.