MAMMALIAN NA+ H+ EXCHANGER GENE FAMILY - STRUCTURE AND FUNCTION STUDIES/

Na+/H+ exchangers are integral plasma membrane proteins that exchange extracellular Na+ for intracellular H+ with a stoichiometry of one for one. They are inhibitable by the diuretic amiloride and have multiple cellular functions, including intracellular pH homeostasis, cell volu me control, and electroneutral NaCl absorption in epithelia. The prese nce of multiple forms of the exchangers was demonstrated by the recent cloning of four mammalian Na+ /H+ exchangers, NHE1, NHE2, NHE3, and N HE4. All of these cloned Na+/H+ exchangers have 10-12 putative transme mbrane helixes and a long cytoplasmic carboxyl domain. Despite the str uctural similarity, these Na+/H+ exchanger isoforms differ in their ti ssue distribution, kinetic characteristics, and response to external s timuli. The present review deals with the recent developments in the m olecular identification of the Na+/H+ exchanger gene family, the funct ional characteristics, and the short-term regulation of Na+/H+ exchang e at molecular and cellular levels.