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JC Fleischhauer, CH Mitchell, DW Stamer, K Peterson-Yantorno, MM Civan; Human Trabecular Meshwork Cell Volume Regulation . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1020.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To study the regulation of volume of trabecular meshwork (TM) cells, which may modify resistance to outflow of aqueous humor, thereby altering intraocular pressure. Methods: Volume, Cl- currents and intracellular Ca2+ activity of cultured human TM cells were studied with calcein fluorescence, whole-cell patch clamping and fura-2 fluorescence, respectively. Results: At physiologic HCO3- concentration, the selective Na+/H+ antiport inhibitor dimethylamiloride reduced isotonic cell volume. Hypotonicity triggered a regulatory volume decrease (RVD), which could be inhibited by the Cl- channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB). The K+-Cl- symport blocker [(dihydro-indenyl)oxy]alkanoic acid (DIOA) also partially inhibited the RVD. Patch-clamp measurements showed that hypotonicity activated an outwardly-rectifying, NPPB-sensitive Cl- channel displaying the permeability ranking Cl- ≷ methylsulfonate ≷ aspartate. 2,3-Butanedione 2-monoxime (BDM) antagonizes actomyosin activity, and both increased baseline Ca2+ concentration and abolished the swelling-activated increase in Ca2+ concentration, but did not affect RVD. Conclusion: Human TM-cells display a Ca2+-independent RVD and their volume is regulated by swelling-activated Cl- channels, K+-Cl- symports and Na+/H+ antiports, in addition to the previously noted Na+-K+-2Cl- symport. This may account for the inability to lower intraocular pressure by blocking Na+-K+-2Cl- cotransport alone. [Support: Swiss National Science Foundation #1037 and Alfred Vogt Foundation, Switzerland Fellowships (JCF), an RPB Career Development Award (WDS), and NIH grants EY013624 (MMC), EY12797 (WDS), EY10009 (CHM), and EY01583 (CHM, MMC)]
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