Na+-H+ exchange in salivary secretory cells is controlled by an intracellular Na+ receptor

It recently has been shown that epithelial Na+ channels are controlled by a receptor for intracellular Na+, a G protein (G(o)), and a ubiquitin-protein ligase (Nedd4), Furthermore, mutations in the epithelial Na+ channel that underlie the autosomal dominant form of hypertension known as Liddle's syndrome inhibit feedback control of Na+ channels by intracellular Na+. Because all epithelia, including those such as secretory epithelia, which do not express Na+ channels, need to maintain a stable cytosolic Na+ concentration ([Na+](i)) despite fluctuating rates of transepithelial Na+ transport, these discoveries raise the question of whether other Na+ transporting systems in epithelia also may be regulated by this feedback pathway, Here we show in mouse mandibular secretory (endpiece) cells that the Na+-H+ exchanger, NHE1, which provides a major pathway for Na+ transport in salivary secretory cells, is inhibited by raised [Na+](i) acting via a Na+ receptor acid G(o). This inhibition involves ubiquitination, but does not involve the ubiquitin protein ligase, Nedd4, We conclude that control of membrane transport systems by intracellular Na+ receptors may provide a general mechanism for regulating intracellular Na+ concentration.