A quantitative analysis of electrolyte exchange in the salivary duct

Abstract

for K ϩ and HCO 3 Ϫ , producing a hypotonic final saliva with no apparent loss in volume. We have developed a tool that aims to understand how the ducts achieve this electrolyte exchange while maintaining the same volume. This tool is part of a larger multiscale model of the salivary gland and can be used at the duct or gland level to investigate the effects of genetic and chemical alterations. In this study, we construct a radially symmetric mathematical model of the mouse salivary gland duct, representing the lumen, the cell, and the interstitium. For a given flow and primary saliva composition, we predict the potential differences and the luminal and cytosolic concentrations along a duct. Our model accounts well for experimental data obtained in wild-type animals as well as knockouts and chemical inhibitors. Additionally, the luminal membrane potential of the duct cells is predicted to be very depolarized compared with acinar cells. We investigate the effects of an electrogenic vs. electroneutral anion exchanger in the luminal membrane on concentration and the potential difference across the luminal membrane as well as how impairing the cystic fibrosis transmembrane conductance regulator channel affects other ion transporting mechanisms. Our model suggests the electrogenicity of the anion exchanger has little effect in the submandibular duct. salivary glands; tubular transport; membrane transport SALIVA IS COMPOSED OF 99% water, and yet that other 1% helps to maintain oral health by providing an appropriate ecological balance in the mouth (45). The basic secretory unit of a salivary gland consists of a cluster of acinar cells and a segment of duct (Fig. 1). The acinar cells secrete an isotonic primary saliva high in Na ϩ and Cl Ϫ but low in K ϩ . These cells produce all of the water found in saliva as the duct is considered to be highly impermeable to water (21). As the fluid travels along the duct, the duct cells exchange Na ϩ and Cl Ϫ for K ϩ and HCO 3 Ϫ , producing a hypotonic final saliva. This electrolyte exchange creates a final saliva that acts as a buffer in the mouth, neutralizing acids and inhibiting caries progression. This hypotonicity also enhances the ability to taste salty foods and nutrient-rich foods (18). Primary saliva production has been modeled by Gin et al. (16) and Palk et al. (37); however, these models do not include any representation of the salivary duct. One aim in studying this system is to provide a quantitative understanding of how hypotonicity is achieved in the mouse submandibular gland duct with no apparent change in saliva volume. It is, to the best of our knowledge, the first quantitative description of a salivary duct and is validated against a variety of experimental data. This model is also a tool that can be used alone or incorporated into a multi-scale model of the salivary gland, spanning from molecular to the tissue level (31,37,47). Depending on the application, either tool can be used to study genetic and chemical alterations, including, but not limited to, sal...

Function and repair of dental enamel – Potential role of epithelial transport processes of ameloblasts

“…Their functional significance has not yet been investigated in ameloblasts. Potassium channels are universally present at the basolateral membrane of secretory epithelia and they play a vital role in controlling the membrane potential and thereby maintaining the driving forces for electrolyte secretion [39,40]. This is particularly important for ameloblasts where large K þ fluxes arise through cotransport and exchange with other ions.…”

Multiscale modelling of saliva secretion

“…Their principal function is to replace NaCl with KHCO 3 , and thus they come equipped with a variety of ion channels on their apical and basolateral membranes (Fig. 4) [24]. Furthermore, secondary saliva is hypotonic with respect to the cell.…”

“…Model variations against data from the wild-type and CFTR knockout mouse secondary saliva [24]. The CFTR knockout mouse model has the CFTR channel deleted.…”

Ae4 (Slc4a9) is an electroneutral monovalent cation-dependent Cl−/HCO3− exchanger

“…Given that Ae4-mediated transport is an electroneutral process (see Fig. 4 ) and assuming the following fixed steady-state ion concentrations for SMG acinar cells (mM): [Cl − ] o = 124.6 ( Mangos et al, 1973 ), [Cl − ] i = 50.1 ( Peña-Münzenmayer et al, 2015 ), [HCO 3 − ] o = 24.7 (serum; Mangos et al, 1973 ), [HCO 3 − ] i = 19 (calculated; Patterson et al, 2012 ), [Na + ] o = 151.6 ( Mangos et al, 1973 ), and [Na + ] i = 15.5 (calculated from rat sublingual acini; Zhang et al, 1993 ), we calculated the Gibbs free energy (ΔG) values that are associated with Ae4-mediated Cl − influx by independently varying the intracellular concentrations of Cl − , Na + , and HCO 3 − , respectively. ΔG values were obtained assuming the following potential stoichiometries that could produce electroneutral Ae4-mediated transport (Cl − :Na + :HCO 3 − ): 1:1:2, 1:2:3, and 2:1:3 ( Eqs.…”