Kinetic analysis of cytosolic ph regulation in alveolar
macrophages: v-atpase-mediated responses to a weak acid.
Bidani, Akhil, and Thomas A. Heming.
Departments of Internal Medicine, and Physiology & Biophysics,
University of Texas Medical Branch, Galveston, Texas 77550-0561
APStracts 2:0027L, 1995.
Three different mechanisms interact to control the cytosolic pH (pHi)
of alveolar macrophages (M[phi]), namely, plasmalemmal vacuolar-type H+
-ATPase (V-ATPase), Na+-H+ exchange, and Na+-independent HCO3--Cl-
exchange. To investigate the activity of plasmalemmal V-ATPase in
alveolar M[phi], we developed a nonlinear mathematical model of pHi
regulation that incorporates the biophysical determinants of pHi and
the fluxes of individual acid-base equivalents. The model was used to
analyze the acid-base responses of rabbit alveolar M[phi] to a weak acid
(propionic acid) under conditions that favored V-ATPase-mediated
effects (presence of 1 mM amiloride and nominal absence of CO2). The
pHi was measured using the fluorescent probe, 2',7'-biscarboxethyl
-5,6-carboxyfluoroscein. M[phi] exposure to propionic acid caused a rapid
fall in pHi. Recovery of pHi after acid-loading varied directly with
the magnitude of the acid-load. Mathematical analyses showed that pHi
recovery was hindered by persistent influx of propionic acid driven,
in turn, by transporter-mediated H+ extrusion and propionate efflux.
Eventually, a new steady-state was established in which propionate
and H+ were cycled out of the M[phi] and propionic acid was recycled into
the cell. As a consequence, model predictions of the rate of V
-ATPase-mediated H+ efflux were almost twice that estimated from
experimental determinations of the initial rate of pHi recovery.
Received 13 October 1994; accepted in final form 14 February
1995.
APS Manuscript Number L292-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 February 1995.