Abstract
Purpose: :
Expression of AQP5 in apical membranes of duct cells suggests that they secrete tear fluid. Moreover, duct cells express apical KCC1, serosal NHE1, AE1, and much higher expression of serosal NKCC1 compared to acinar cells. This suggests that duct cells could have similar or even greater fluid transport capability than acinar cells. However, the role of an apical KCC1 cotransporter in fluid secretion is unclear. So, a mathematical model of duct cell was developed examine fluid secretion and cell volume and pH regulation in an isolated model cell and a model cell with a luminal compartment.
Methods: :
The model is based on mass conservation, electroneutrality constraints, and includes kinetic models of Na+-K+-ATPase, NKCC1, KCC1, NHE1, AE1, CO2 hydration, and passive fluxes of ions, non-electrolytes and water. The effects of muscarinic stimulation to enhance apical Cl- and K+ permeabilities and NHE1 activity are also included, as are the effects of cell volume changes on the NKCC1 and KCC transporters.
Results: :
In single-cell mode, pH recovery from acid loading is demonstrated, which can be reduced by NHE1 inhibition by amiloride. Exposure to carbachol causes cellular alkalization due to increased NHE1 activity, consistent with experimental data. In compartment mode, muscarinic stimulation causes secretion of hypertonic fluid from the apical membrane and cell volume reduction, which inactivates the volume-sensitive KCC1 cotransporter on the apical membrane.
Keywords: lacrimal gland • computational modeling • ion transporters