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Am J Physiol Cell Physiol 280: C1521-C1530, 2001;
0363-6143/01 $5.00
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Vol. 280, Issue 6, C1521-C1530, June 2001

Model of ionic transport for bovine ciliary epithelium: effects of acetazolamide and HCO<UP><SUB>3</SUB><SUP>−</SUP></UP>

Chi-Ho To1, Chi-Wai Do1, Aldo C. Zamudio2, and Oscar A. Candia2,3

1 Laboratory of Ocular Physiology and Biochemistry, Department of Optometry and Radiography, Hong Kong Polytechnic University, Hung Hom, Hong Kong; and Departments of 2 Ophthalmology and 3 Physiology and Biophysics, Mount Sinai School of Medicine, New York, New York 10029

The possible existence of transepithelial bicarbonate transport across the isolated bovine ciliary body was investigated by employing a chamber that allows for the measurement of unidirectional, radiolabeled fluxes of CO2 + HCO<UP><SUB>3</SUB><SUP>−</SUP></UP>. No net flux of HCO<UP><SUB>3</SUB><SUP>−</SUP></UP> was detected. However, acetazolamide (0.1 mM) reduced the simultaneously measured short-circuit current (Isc). In other experiments in which 36Cl- was used, a net Cl- flux of 1.12 µeq · h-1 · cm-2 (30 µA/cm2) in the blood-to-aqueous direction was detected. Acetazolamide, as well as removal of HCO<UP><SUB>3</SUB><SUP>−</SUP></UP> from the aqueous bathing solution, inhibited the net Cl- flux and Isc. Because such removal should increase HCO<UP><SUB>3</SUB><SUP>−</SUP></UP> diffusion toward the aqueous compartment and increase the Isc, this paradoxical effect could result from cell acidification and partial closure of Cl- channels. The acetazolamide effect on Cl- fluxes can be explained by a reduction of cellular H+ and HCO<UP><SUB>3</SUB><SUP>−</SUP></UP> (generated from metabolic CO2 production), which exchange with Na+ and Cl- via Na+/H+ and Cl-/HCO<UP><SUB>3</SUB><SUP>−</SUP></UP> exchangers, contributing to the net Cl- transport. The fact that the net Cl- flux is about three times larger than the Isc is explained with a vectorial model in which there is a secretion of Na+ and K+ into the aqueous humor that partially subtracts from the net Cl- flux. These transport characteristics of the bovine ciliary epithelium suggest how acetazolamide reduces intraocular pressure in the absence of HCO<UP><SUB>3</SUB><SUP>−</SUP></UP> transport as a driving force for fluid secretion.

aqueous humor secretion; chloride fluxes; bicarbonate fluxes; Ussing chamber; short-circuit current


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