The Role of the Tight Junction in Paracellular Fluid Transport across Corneal Endothelium. Electro-osmosis as a Driving Force |
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Authors: | J Fischbarg FPJ Diecke P Iserovich A Rubashkin |
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Institution: | (1) Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, 630 W. 168th St., New York, NY 10032, USA;(2) Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, 630 W. 168th St., New York, NY 10032, USA;(3) Department of Pharmacology and Physiology, UMDNJ, New Jersey Medical School, 185 South Orange Ave., Newark, NJ 07103-2714, USA;(4) Institute of Cytology, Russian Academy of Sciences, Tikhoretskii pr 4, St. , Petersburg, 194064, Russia |
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Abstract: | The mechanism of epithelial fluid transport is controversial and remains unsolved. Experimental difficulties pose obstacles
for work on a complex phenomenon in delicate tissues. However, the corneal endothelium is a relatively simple system to which
powerful experimental tools can be applied. In recent years our laboratory has developed experimental evidence and theoretical
insights that illuminate the mechanism of fluid transport across this leaky epithelium. Our evidence points to fluid being
transported via the paracellular route by a mechanism requiring junctional integrity, which we attribute to electro-osmotic
coupling at the junctions. Fluid movements can be produced by electrical currents. The direction of the movement can be reversed
by current reversal or by changing junctional electrical charges by polylysine. Aquaporin 1 (AQP1) is the only AQP present
in these cells, and its deletion in AQP1 null mice significantly affects cell osmotic permeability but not fluid transport,
which militates against the presence of sizable water movements across the cell. By contrast, AQP1 null mice cells have reduced
regulatory volume decrease (only 60% of control), which suggests a possible involvement of AQP1 in either the function or
the expression of volume-sensitive membrane channels/transporters. A mathematical model of corneal endothelium predicts experimental
results only when based on paracellular electro-osmosis, and not when transcellular local osmosis is assumed instead.
Our experimental findings in corneal endothelium have allowed us to develop a novel paradigm for this preparation that includes:
(1) paracellular fluid flow; (2) a crucial role for the junctions; (3) hypotonicity of the primary secretion; (4) an AQP role
in regulation and not as a significant water pathway. These elements are remarkably similar to those proposed by the Hill
laboratory for leaky epithelia. |
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Keywords: | Local osmosis Permeability Aquaporin Knockout Model |
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