Aquaporins and fluid transport: an evolving relationship.

How epithelia transport fluid is controversial and remains undetermined. Two routes are possible: (1) via cell membranes and their aquaporins, or (2) paracellular. Our laboratory has recently developed experimental evidence and theoretical insights for fluid transport across corneal endothelium, a leaky epithelium. 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 sizable water movements across the cell. In contrast,AQP1 null mice cells have reduced regulatory volume decrease (only 60% of control), which suggests an AQP1 role in either the function or the expression of volume-sensitive membrane channels/transporters. Fluid movements can be produced by electrical currents, and the direction of the movement can be reversed by current reversal or by changing junctional electrical charges with polylysine. A mathematical model of corneal endothelium predicts experimental observations only when based on paracellular electro-osmosis. Our novel paradigm for this preparation includes: (1) paracellular fluid flow; (2) a crucial role for the junctions as a site for electro-osmosis; (3) hypotonicity of the primary secretion; (4) an AQP role in regulation and not as a significant water pathway.