Na+/H+ exchangers (NHE) of mammalian cells are plasma membrane intrinsic proteins mediating exchange of N+ and H+ ions in various tissues. The NHE catalyzes the electroneural transport of extracellular Na+ for intracellular H+. They play a major role in regulation of intracellular pH (pHi) in addition to trans-cellular absorption of Na+, cell volume regulation and possibly in cell proliferation. These primary functions of the Na+/H+ exchanger have been related to many pathophysiological states, include hypertension, organ growth and hypertrophy, regression of cancer and renal intestinal disorders. Five NHE isoforms (NHE1-5) have been cloned so far. They are all similar in their primary structure and predicted to have 10-12 transmembrane domains. The COOH-terminals of NHE1, NHE2 and NHE3 are intracellular. NHE1 (rat/mouse; 820aa; human 815aa; chromosome 1 p35-36.1) is 'House Keeper' and is expressed ubiquitously in all tissues. It is implicated in pH homeostasis, volume regulation and probably cell proliferation. It is expressed on basolateral surface of several epithelia (1).
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