Transepithelial Na⁺ transport and the intracellular fluids: A computer study

Computer simulations of tight epithelia under three experimental conditions have been carried out, using the rheogenic nonlinear model of Lew, Ferreira and Moura (Proc. Roy. Soc. London. B206:53-83, 1979) based largely on the formulation of Koefoed-Johnsen and Ussing (Acta Physiol. Scand. 42:298-308, 1958). First, analysis of the transition between the short-circuited and open-circuited states has indicated that (i) apical Cl^- permeability is a critical parameter requiring experimental definition in order to analyze cell volume regulation, and (ii) contrary to certain experimental reports, intracellular Na⁺ concentration (c_Na^c) is expected to be a strong function of transepithelial clamping voltage. Second, analysis of the effects of lowering serosal K⁺ concentration (c_K^s) indicates that the basic model cannot simulate several well-documented observations; these defects can be overcome, at least qualitatively, by modifying the model to take account of the negative feedback interaction likely to exist between the apical Na⁺ permeability and c_Na^c. Third, analysis of the effects induced by lowering mucosal Na⁺ concentration (c_Na^m) strongly supports the concept that osmotically induced permeability changes in the apical intercellular junctions play a physiological role in conserving the body's stores of NaCl. The analyses also demonstrate that the importance of Na⁺ entry across the basolateral membrane is strongly dependent upon transepithelial potential, c_Na^m and c_K^s; under certain conditions, net Na⁺ entry could be appreciably greater across the basolateral than across the apical membrane.