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Description
We constructed a dynamical model of a salivary gland acinar cell with the objective of investigating the role of two plasma membrane (PM) anion exchangers, the Ae2 (Slc4a2) and Ae4 (Slc4a9), in primary fluid secretion. Transepithelial chloride (Cl$^-$) movement drives water transport in salivary gland acinar cells. Basolateral PM mechanisms accumulate Cl$^-$ to levels well above its electrochemical equilibrium. Following an increase in the intracellular concentration of calcium (Ca$^{2+}$), a Cl$^-$ efflux through apical Ca$^{2+}$-dependent Cl$^-$ channels (TMeM16a) generates a transepithelial osmotic gradient. Water follows this gradient by osmosis. Cl$^-$ uptake via basolateral co-transporters (Nkcc1), provides the major force for generating fluid secretion in acinar cells. Despite this, Nkcc1 knockout experiments saw an approximate 70$\%$ decrease in gland salivary rate. The residual secretion is bicarbonate (HCO$_3^-$) dependent and involves two sodium/proton (Nhe1) paired Cl$^-$/HCO$_3^-$ anion exchangers, the Ae2 and the Ae4. Experiments revealed that Ae4 knockout mice displayed a decreased gland fluid secretion ($\sim$ 30$\%$ of the control fluid flow rate) whilst Ae2 knockout mice gland salivation remained intact. The reason behind the results remains a controversial topic. Our model's results reproduce and support the experimental observations. More importantly, they suggest that the Ae4 cotransport of monovalent cations is likely to be important in establishing the osmotic gradient necessary for optimal transepithelial fluid movement.
