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Abstract #5584 Published in IGR 2-1
Intracellular Cl regulates Na-K-Cl cotransport activity in human trabecular meshwork cells
Putney LK; Vibat CR; O'Donnell MEAmerican Journal of Physiology 1999; 277:C373-C383
The trabecular meshwork (TM) of the eye plays a central role in modulating intraocular pressure by regulating aqueous humor outflow, although the mechanisms are largely unknown. The authors and others have shown previously that aqueous humor outflow facility is modulated by conditions that alter TM cell volume. They have also shown that the Na-K-Cl cotransport system is a primary regulator of TM cell volume and that its activity appears to be coordinated with net efflux pathways to maintain steady-state volume. However, the cellular mechanisms that regulate cotransport activity and cell volume in TM cells have yet to be elucidated. The present study was conducted to investigate the hypothesis that intracellular Cl concentration ((Cl)i) acts to regulate TM cell Na-K-Cl cotransport activity, as has been shown previously for some other cell types. The authors demonstrate here that the human TM cell Na-K-Cl cotransporter is highly sensitive to changes in (Cl)i. Their findings reveal a marked stimulation of Na-K-Cl cotransport activity, assessed as ouabain-insensitive, bumetanide-sensitive K influx, in TM cells following preincubation of cells with Cl-free medium as a means of reducing (Cl)i. In contrast, preincubation of cells with media containing elevated K concentrations as a means of increasing (Cl)i results in inhibition of Na-K-Cl cotransport activity. The effects of reducing (Cl)i, as well as elevating (Cl)i, on Na-K-Cl cotransport activity are concentration dependent. Furthermore, the stimulatory effect of reduced (Cl)i is additive with cell-shrinkage-induced stimulation of the cotransporter. These studies also show that TM cell Na-K-Cl cotransport activity is altered by a variety of Cl channel modulators, presumably through changes in (Cl)i. These findings support the hypothesis that regulation of Na-K-Cl cotransport activity, and thus cell volume, by (Cl)i may participate in modulating outflow facility across the TM.
Dr. L.K. Putney, Department of Human Physiology, School of Medicine, University of California, Davis, CA 95616-8644, USA
Classification:
2.5 Meshwork (Part of: 2 Anatomical structures in glaucoma)
4 Tissue culture of ocular cells