title: Exploration of apical sodium transport mechanisms in an epithelial model by network thermodynamic simulation of the effect of mucosal sodium depletion: II. An apical sodium channel and amiloride blocking.
abstract: This paper is the second part of a modeling study on apical sodium transport mechanisms in tight epithelia. In the first part (this issue) we explored three expressions for the apical membrane sodium permeability (PapNa) and showed that only a PapNa which varies as a function of sodium concentration allows simulation of the well known saturation of the short-circuit current with increasing mucosal sodium concentration. However, the ad hoc expressions used have no mechanistic interpretation. We show here that if, instead of an ad hoc expression, one includes a one-site, two-barrier sodium channel in the apical membrane, the model also simulates this saturation. In addition, the equivalent apical sodium permeability computed from the simulations appears to be very similar to the phenomenological equation used by Fuchs et al. (1977) to fit the decrease of the apical sodium permeability with increasing mucosal sodium. The apical sodium channel simulated here is thus a possible mechanism for the feedback effect of the mucosal and intracellular sodium concentrations on the apical sodium permeability. This channel also allows the simulation of the competitive inhibition of the sodium current by amiloride, and the concomitant inhibition of the apical sodium permeability.
mesh_terms: D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003198:Computer Simulation; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism; D011336:Probability; D012964:Sodium / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D007473:Ion Channels; D000584:Amiloride; D012964:Sodium