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Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, New York 10021
A mathematical model of the outer medullary
collecting duct (OMCD) has been developed, consisting of
-intercalated cells and a paracellular pathway, and which includes
Na+, K+, Cl
,
HCO3
, CO2, H2CO3,
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 HCO3
exit is via a
conductive pathway and via the Cl
/HCO3
exchanger, AE1. To represent AE1, a kinetic model has been developed based on transport studies obtained at 38°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 HCO3
and HPO42
, as well as peritubular NH3.
Thus, buffer availability is unlikely to exert a regulatory role in
total proton secretion by this tubule segment.
proton-potassium-activated adenosinetriphosphatase; AE1; urine acidification; ammonia transport
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