The Role of NA+/H+ Exchange and Intracellular pH Changes in Fertilization

Research over the last ten years indicates that one of the earliest responses to mitogenic signals is often a rise in intracellular pH (pH_i) mediated by an amiloride-sensitive Na⁺/H⁺ exchange process. Knowledge of this phenomenon and its potential importance for growth regulation, first came from studies on the fertilization process in sea urchin eggs. In these eggs a prodigious amount of acid is released from the cells shortly after fertilization, and it was realized, just 11 years ago, that the acid release was actually an amiloride-sensitive Na⁺/H⁺ exchange process which alkalized the cytoplasm. Experimental interventions were devised to assess the effects of preventing alkalinization, as by deletion of sodium from the medium or by incubating the eggs in amiloride. Also, it was found that weak bases such as ammonia would directly raise pH_i. This use of Na⁺-free media, amiloride, and ammonia has provided experimental protocols, which have since been extrapolated to many other cell systems, to delineate the general role of Na⁺/H⁺ exchange and pH_i increases for cell function (see reviews in References 1 to 3).