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W. Huang, C. Clausen, P. Brink, B. Walcott, L. C. Moore; Mathematical Model of Fluid Secretion by Lacrimal Acinar and Duct Cells. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4167.
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Lacrimal duct and acinar cells (AC) express similar arrays of membrane transport proteins, which suggest that duct cells (DC) secrete tear fluid. One difference in DC is the presence on the apical membrane of the electroneutral KCC1 transporter, a secretory pathway that may be important in the generation and maintenance of the high K+ and Cl- concentrations in tear fluid. We developed a mathematical model of the lacrimal DC to examine the role of the KCC1 transporter and apical membrane water permeability in the formation of hypertonic tear fluid with high [K+]. This model was combined with an existing AC model.
The DC model is based on mass conservation, electroneutrality constraints, and includes kinetic models of Na+-K+-ATPase, NKCC1, KCC1, NHE1, AE1, pNBC1, CO2 hydration, passive fluxes of ions, non-electrolytes and water. The effects of muscarinic stimulation to enhance apical Cl- and K+ permeabilities are included, as are the effects of cell volume changes on the NKCC1 and KCC transporters activities. The model includes a fixed-volume apical lumen that drains secretions from model AC; the DC apical ion and water fluxes then adds to tear flow and modifies the fluid secreted by the AC.
At rest, DC cytosolic [Cl-] is held above equilibrium by the basolateral NKCC1, DC fluid secretion is low and KCC1 transport elevates luminal [K+]. When stimulated, DC K+ and Cl– , fluxes are mostly passive and water secretion rises. Luminal flow increases ~10 fold and the exiting fluid is hypertonic with ~ 40 mM K+. The predicted final tear composition and the relative increase in flow agree with published data.
Lacrimal DC and AC both secrete high [K+] hypertonic fluid. The apical KCC1 transporter in DC is needed to keep luminal fluid [K+] high at rest. Low junctional ion permeabilities are also needed to keep luminal [K+] high. The formation of hypertonic tear fluid both at rest and when stimulated requires that apical membrane water permeability is very much lower than that of the basolateral membrane.
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