Regulation of Na+/H+ Exchange: Role of Ca+2

Since the initial discovery ^{1 , 2} that there exists a plasma membrane transport system whose purpose is to exchange external Na⁺ ions for internal protons in an effort to regulate intracellular pH, it has been recognized that this system can be activated by external agents. In their initial description of the Na⁺/H⁺ exchanger in sea urchin eggs, Johnson et al. ¹ demonstrated that this transport system is activated when eggs are fertilized, resulting in an increase in Na⁺ influx along with an increase in proton extrusion. Soon after, studies by Smith and Rozengurt ^{3 , 4} in cultured fibroblasts and by Koch and Leffert ⁵ in cultured liver cells described the activation of the Na⁺/H⁺ exchanger by mitogenic factors. These demonstrations, that the activity of the Na⁺/H⁺ exchanger could be stimulated by external agents, led to a a whole new series of studies seeking to define the mechanism by which this transport system is regulated. Many of these studies focused on the possible involvement of second messengers in the activation process.