Molecular Properties, Kinetics and Regulation of Mammalian Na+/H+ Exchangers

Na+/H+exchange was first described by Murer, Hopfer and Kinne [19] in renal brush border membrane vesicles. This process is mediated by Na+/H+exchangers which catalyze the exchange of extracellular Na+for intracellular H with a stoichiometry of 1:1. Na+/H+exchangers have multiple functions, including pH homeostasis, volume regulation, cell proliferation, and transcellular Na+absorption [reviewed in 12]. In no cell is it the only mechanism for any one of these functions. For instance, multiple mechanisms of pH homeostasis are present in most eukaryotic cells including a c┌/HCO3-exchanger, a NaHCO3co-transporter, a Na+- dependent cr/HCO3-exchanger and multiple mechanisms of hT extrusion [reviewed in 15], including the H-K-ATPase pump. In this review, we will focus on recent advances in identification and understanding of the structure/function relationships and acute protein kinase regulation of members of the mammalian Na+/H+exchanger gene family.