Influx mechanisms for Na+ and Cl− across the brush border membrane of leaky epithelia: A model and microelectrode study

Abstract

This paper presents a numerical model for the movement of Na⁺, K⁺, Cl⁻, H⁺ and HCO ₃ ⁻ in a leaky epithelium. The model describes the active transport of Na⁺ and K⁺ at the serosal membrane and electrodiffusive permeation across the mucosal, serosal and junctional pathways. The model accounts for H⁺ and HCO ₃ ⁻ production in the cell. The influx of Na⁺ and Cl⁻ is assumed to occur mainly via Na/H and Cl/HCO₃ exchange. The behavior of the cell, with this influx mechanism, is compared to a cell with an obligatory neutral coupled influx of Na⁺ and Cl⁻. All parameters are obtained from the literature, primarily from studies utilizing theNecturus gallbladder. The analysis shows (i) that it is virtually impossible insteady-state experiments to distinguish between cells with Na/H−HCO₃/Cl transport and cells with Na/Cl transport mechanisms. (ii) Thatnonsteady-state experiments can decide whether Na/H−HCO₃/Cl or Na/Cl transport mechanisms mediate the influx of salt. A comparison between studies with ion-selective microelectrodes and the model predictions indicates that the influx of Na⁺ and Cl⁻ is mediated by Na/H−HCO₃/Cl transport when the external solutions contain CO₂ and HCO₃. (iii) The model also explains the diuretic effects of furosemide and carbonic anhydrase inhibitor, as well as the stimulatory effects on salt transport of elevated levels of HCO ₃ ⁻ at a constant pH. (iv) The model fails to explain some experiments performed in HCO₃/CO₂-free media and some experiments using inhibitors.