MOLECULAR PHYSIOLOGY OF VERTEBRATE NA+ H+ EXCHANGERS/

This review describes recent progress concerning the molecular aspects of the Na+/H+ exchanger. The Na+/H+ exchanger is an important regulat or for intracellular pH, cell volume, and transepithelial Na+ transpor t. It exists in virtually all cells with cell type-dependent pattern o f isoform expression, and it is regulated in response to a variety of extracellular stimuli, among them not only agonists such as growth fac tors and hormones but also mechanical stimuli such as osmotic stress a nd cell spreading. Thus this transporter is also an excellent model to study the signal transduction. Since the first molecular cloning of t he Na+/H+ exchanger, detailed studies revealed many interesting featur es of this transporter. At present, at least five different isoforms o f the Na+/H+ exchanger are known. These isoforms differ in tissue loca lization, sensitivity of inhibitors, and mode of transcriptional and p osttranscriptional regulation, allowing them to participate in differe nt physiological processes. We have only started to understand an intr iguing mechanism underlying these functional differences among the exc hanger isoforms. Because the Na+/H+ exchanger is relatively simple in terms of its kinetic features, e.g., a simple 1:1 stoichiometry of Na and H+ and no input of metabolic energy such as ATP hydrolysis, the s tudy of its structural and mechanistic aspects would also serve as a g ood model to understand the general mechanism of Various ion transport ers.