Osmotic activation of the Na+/H+ antiporter during volume regulation.

Introduction Cellular water content, which accounts for 70% of the cellular mass, is the main determinant of cell volume. In animal cells, which are devoid of rigid walls, it is generally accepted that the water content is dictated by the amount of osmotically active cellular particles. Inorganic ions constitute a major fraction of the cellular osmolytes. It is therefore not surprising that changes in the cellular content of these ions underlie the homeostatic processes whereby many cell types regulate their volume. Many cells maintain their size despite changes in the tonicity of the medium. Thus, osmotically shrunken cells reswell towards their original volume by taking up Na+ and CI-, which are rapidly followed by osmotically obliged water. The purpose of this report is to briefly summarize our current knowledge of the mechanisms underlying this regulatory volume increase (RVI) and to discuss some recent findings from our laboratory. Net volume gain during RVI is associated with an increased content of both Na+ and K + , attributable primarily to enhanced influx rates (see [l-31 for reviews). The stimulated K + influx is virtually eliminated by cardiac glycosides, indicating translocation via the Na+/K+ pump. Importantly, while the glycosides inhibit K + uptake, they do not preclude RVI. Under these conditions, the volume gain persists but is attributable almost entirely to uptake of Na+, accompanying anions and water. These observations suggested that Na+ influx is the primary phenomenon in RVI and that exchange of Na+ for K + , mediated by the pump, is a secondary process.