Compartmental efflux analysis: an evaluation of the technique and its limitations

Efflux analysis is an established tool for characterizing the exchange properties of multicomponent systems. In this report, we have simulated several three- and four-compartment systems with error-free and imperfect data, the errors being designed to mimic actual, nonbiological variability in isotope efflux studies. The data sets were analyzed using computerized nonlinear regression techniques to identify the important aspects of actual experimental design (uptake times, efflux collection schedules, and total efflux times), and to consider the possibility that a properly designed and executed experiment might fail to resolve compartmentation correctly. The results showed that for any of the systems simulated, including those with error-free four-component data, a reasonable three-component fit was obtainable. Resolution of the additional compartment was not always possible. In correctly resolved systems, failure to estimate the correct decay constants was common, especially when the half-times were separated by less than an order of magnitude. We conclude that efflux analysis, by itself, lacks the power to provide reliable information about multicompartment systems.