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

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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.