A mathematical model of the outer medullary collecting duct of the rat.

A mathematical model of the outer medullary collecting duct (OMCD) has been developed, consisting of alpha-intercalated cells and a paracellular pathway, and which includes Na(+), K(+), Cl(-), HCO(3)(-), CO(2), H(2)CO(3), phosphate, ammonia, and urea. Proton secretion across the luminal cell membrane is mediated by both H(+)-ATPase and H-K-ATPase, with fluxes through the H-K-ATPase given by a previously developed kinetic model (Weinstein AM. Am J Physiol Renal Physiol 274: F856-F867, 1998). The flux across each ATPase is substantial, and variation in abundance of either pump can be used to control OMCD proton secretion. In comparison with the H(+)-ATPase, flux through the H-K-ATPase is relatively insensitive to changes in lumen pH, so as luminal acidification proceeds, proton secretion shifts toward this pathway. Peritubular HCO(3)(-) exit is via a conductive pathway and via the Cl(-)/HCO(3)(-) exchanger, AE1. To represent AE1, a kinetic model has been developed based on transport studies obtained at 38 degrees C in red blood cells. (Gasbjerg PK, Knauf PA, and Brahm J. J Gen Physiol 108: 565-575, 1996; Knauf PA, Gasbjerg PK, and Brahm J. J Gen Physiol 108: 577-589, 1996). Model calculations indicate that if all of the chloride entry via AE1 recycles across a peritubular chloride channel and if this channel is anything other than highly selective for chloride, then it should conduct a substantial fraction of the bicarbonate exit. Since both luminal membrane proton pumps are sensitive to small changes in cytosolic pH, variation in density of either AE1 or peritubular anion conductance can modulate OMCD proton secretory rate. With respect to the OMCD in situ, available buffer is predicted to be abundant, including delivered HCO(3)(-) and HPO(4)(2-), as well as peritubular NH(3). Thus, buffer availability is unlikely to exert a regulatory role in total proton secretion by this tubule segment.