A Mathematical Model of ENaC and Slc26a6 Regulation by CFTR in Salivary Gland Ducts.

Cystic Fibrosis (CF) is a genetic disease caused by the mutations of CFTR, the cystic fibrosis transmembrane conductance regulator gene. Cftr is a critical ion channel expressed in the apical membrane of mouse salivary gland striated duct cells. Although Cftr is primarily a Cl- channel, its knockout leads to higher salivary Cl- and Na+concentrations and lower pH. Mouse experiments show that the activation of Cftr up-regulates ENaC (Epithelial Na+Channel) protein expression level and Slc26a6 (a 1Cl- : 2HCO3- exchanger of the solute carrier family) activity. Experimentally, it is difficult to predict how much the co-regulation effects of CFTR contribute to the abnormal Na+ , Cl- and HCO3- concentrations and pH in CF saliva. To address this question we construct a wild-type mouse salivary gland model, and simulate CFTR knockout by altering the expression levels of CFTR, ENaC and Slc26a6. By reproducing the in-vivo and ex-vivo final saliva measurements from wild-type and CFTR knockout animals, we obtain computational evidence that ENaC and Slc26a6 activities are down-regulated in CFTR knockout in salivary glands.