Model of ionic transport for bovine ciliary epithelium: effects of acetazolamide and HCO.
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. No net flux of HCO was detected. However, acetazolamide (0.1 mM) reduced the simultaneously measured short-circuit current (I(sc)). In other experiments in which (36)Cl- was used, a net Cl- flux of 1.12 microeq. h(-1). cm(-2) (30 microA/cm(2)) in the blood-to-aqueous direction was detected. Acetazolamide, as well as removal of HCO from the aqueous bathing solution, inhibited the net Cl- flux and I(sc). Because such removal should increase HCO diffusion toward the aqueous compartment and increase the I(sc), 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 (generated from metabolic CO2 production), which exchange with Na+ and Cl- via Na+/H+ and Cl-/HCO exchangers, contributing to the net Cl- transport. The fact that the net Cl- flux is about three times larger than the I(sc) 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 transport as a driving force for fluid secretion.
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Laboratory of Ocular Physiology and Biochemistry, Department of Optometry and Radiography, Hong Kong Polytechnic University, Hung Hom, Hong Kong.
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Zamudio
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D000086:Acetazolamide / Q000494:pharmacology*; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D001639:Bicarbonates / Q000493:pharmacokinetics*; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002250:Carbon Radioisotopes; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002417:Cattle; D002924:Ciliary Body / Q000166:cytology* / Q000378:metabolism; D015194:Diffusion Chambers, Culture; D004847:Epithelial Cells / Q000378:metabolism*; D066298:In Vitro Techniques; D007429:Intraocular Pressure / Q000502:physiology; D011189:Potassium Chloride / Q000493:pharmacokinetics; D012965:Sodium Chloride / Q000493:pharmacokinetics
D001639:Bicarbonates; D002250:Carbon Radioisotopes; D002257:Carbonic Anhydrase Inhibitors; D012965:Sodium Chloride; D011189:Potassium Chloride; D000086:Acetazolamide