Influx mechanisms for Na+ and Cl- across the brush border membrane of leaky epithelia: a model and microelectrode study.

This paper presents a numerical model for the movement of Na+, K+, Cl-, H+ and HCO3- 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 HCO3- 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 the Necturus gallbladder. The analysis shows (i) that it is virtually impossible in steady-state experiments to distinguish between cells with Na/H - HCO3/Cl transport and cells with Na/Cl transport mechanisms. (ii) That nonsteady-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 HCO3- at a constant pH. (iv) The model fails to explain some experiments performed in HCO3/Co2-free media and some experiments using inhibitors.