Control of Na+ transport in salivary duct epithelial cells by cytosolic Cl- and Na+

The duct cells of the mandibular glands of mice (and many other mammalian salivary glands) absorb NaCl from an isotonic, Na+-rich primary saliva, formed by the gland's secretory endpieces, utilising an amiloride-sensitive Na+ channel in the apical (luminal) domain of the plasma membranes. The present study focuses on the mechanisms whereby the apical membrane Na+ conductance is controlled so that the rate of Na+ influx from lumen to cytosol via the Na+ channels is matched to the rate of Na+ extrusion from cytosol to interstitium via the basolateral Na+-K+-ATPase (so called homocellular regulation or epithelial cross-talk). Our results show that the apical membrane Na+ conductance is not controlled by a sensor of extracellular (luminar) Na+, as has been previously believed, but by sensors of cytosolic Na+ and Cl- which down-regulate the Na+ channels when the cytosolic concentration of either ion increases. These effects of cytosolic Na+ and Cl- are mediated, respectively, by G proteins of the G(i) and G(o) subclasses.