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Mathematical model of lacrimal acinar cell pH and volume regulation
Author(s) -
Huang Wei Chieh,
Clausen Chris,
Brink Peter,
Walcott Benjamin,
Moore Leon C
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.933.11
Subject(s) - cotransporter , chemistry , ion transporter , secretion , biophysics , bumetanide , transporter , intracellular , sodium–hydrogen antiporter , homeostasis , sodium , electrolyte , intracellular ph , cytosol , biochemistry , microbiology and biotechnology , membrane , biology , enzyme , organic chemistry , electrode , gene
When stimulated, lacrimal acinar cells (LAC) secrete K + , Cl − and water. This is associated with cell shrinkage, and activation of the Na + ‐K + ‐2Cl − cotransporter (NKCC1), and of the Na + ‐H + (NHE1) and Cl − ‐HCO 3 − (AE) exchangers. These transporters pump Na + and Cl − into the cell to maintain tear secretion. However, experiments have shown that LAC ion transport is relatively insensitive to inhibition of either the NHE1 or NKCC1 transporters. In this study, we used a mathematical model of LAC ion and water transport to examine interactions between tear secretion, cell volume (CV) regulation and pH homeostasis. The model is based on mass conservation, electroneutrality constraints, and includes kinetic models of Na + ‐K + ‐ATPase, NKCC1, the K + ‐Cl − cotransporter (KCC), NHE1, AE, 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 CV changes on the NKCC1 and KCC transporters. During secretion, the model predicts increased NHE1 and AE ion transport when NKCC1 is inhibited, and higher NKCC1 uptake when NHE1 in inhibited. In both cases, the compensatory changes are driven by reduced cell [Cl − ]. The results suggest that interactions of the transporters in tear secretion, CV and pH control are in part mediated by altered cytosolic Cl − levels. Supported by NIH grant EY14604.