Acid/base transport in a model of the proximal tubule brush border:
impact of carbonic anhydrase.
Krahn, Thomas A., Alan M. Weinstein.
Department of Physiology and Biophysics, Department of Medicine,
Cornell University Medical College
APStracts 2:0155F, 1995.
A mathematical model of the brush border of the proximal tubule (Krahn
et al., 1994) has been extended by the inclusion of CO2 and H2CO3 as
diffusible species, and by the inclusion of finite rate constants for
the hydration of CO2. This permits the simulation of carbonic
anhydrase (CA) activity and its inhibition. We confirm the result of
our previous paper that in the presence of CA, the unstirred layer
has only a modest effect on the observed formic acid permeability. CA
inhibition results in disequilibrium pH gradients, and the effect of
these gradients on formic acid permeability depends on the presence
of other membrane transport proteins. We also examined the impact of
CA activity on the flux of total CO2 through the brush border. Under
physiologic conditions, CA inhibition depressed NaHCO3 reabsorption
through the brush border, by interfering with the HCO3- facilitated
diffusion of CO2. However, the determination of brush border CO2
permeability, using an imposed CO2 gradient, was relatively
uninfluenced by CA activity. Finally, we inserted a kinetic
representation of the Na-/H- exchanger into the brush border model.
Even when luminal and cytosolic diffusion coefficients were increased
1000-fold, there was no effect on brush border Na- flux. This
suggests that variations in the unstirred layer cannot be responsible
for the flow dependence of Na- reabsorption.
Received 5 June 1995; accepted in final form 21 August 1995.
APS Manuscript Number F179-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.