Regulation of renal ion transport and cell growth by sodium

Intracellular sodium has been implicated in a variety of cellular processes including regulation of Na+-K+-ATPase activity, mitogen-induced cell growth, and proliferation and stimulation of Na+-K+-ATPase by aldosterone. In renal epithelial cells a rise in sodium uptake across the apical membrane increases intracellular sodium concentration, which in turn stimulates the turnover rate of Na+-K+-ATPase and thereby enhances sodium efflux across the basolateral membrane. A prolonged increase in sodium uptake causes dramatic hypertrophy and hyperplasia and a rise in the quantity of Na+-K+-ATPase in the basolateral membrane. These structural and functional changes occur in the kidney in the absence of alterations in plasma aldosterone and vasopressin levels. Several mitogens induce growth and proliferation by initiating a cascade of events, which include a rise in intracellular sodium. Accordingly, an increase in the sodium concentration within renal epithelial cells may elicit a "mitogen-like" effect by initiating the cascade at the sodium step, even in the absence of a mitogen. A rise in cell sodium may also stimulate the production of autocrine growth factors that directly or indirectly regulate cell growth and proliferation, by modifying the response to mitogens or to changes in the ionic composition of the extracellular fluid. In this review we will examine the evidence that supports a role for intracellular sodium in regulating these cellular events in renal epithelial cells.