Chapter 7 Activation of the Na+-H+ Antiport by Changes in Cell Volume and by Pnorbol Esters; Possible Role of Protein Kinase

Publisher Summary A system that catalyzes the exchange of Na + for H + appears to be a ubiquitous feature of the plasma membrane of nucleated mammalian cells. The Na + –H + exchange can be detected in rat thymocytes following acid loading, a procedure that greatly increases its activity. A method for controlled acid loading involves the use of nigericin, an electroneutral K + –H + exchanging ionophore. Under certain conditions, osmotically shrunken cells regain near-normal volumes by a process known as regulatory volume increase (RVI). Osmotic shrinking produces an activation of the Na + –H + antiport in blood and thymic lymphocytes. In an earlier study, the mechanism of activation of Na + –H + exchange by osmotic shrinking was evaluated by comparing the kinetic parameters of transport in resting (isotonic) and hyperosmotically stressed cells. This chapter describes the mechanism of activation for the stimulation of Na + –H + exchange by phorbol esters. Phorbol diesters are the structural analogs of diacylglycerols that are thought to be the physiological activators of protein kinase C. When measured as the cytoplasmic alkalinization, the activations of the Na + –H + exchanger induced by shrinking and by phorbol esters are remarkably similar. Shrinking activates a different type of protein kinase that in turn stimulates phosphoinositide turnover.