Sodium/Hydrogen Exchanger 3 (NHE3)

An apical membrane Na+/H+ exchanger is involved in transepithelial, electroneutral Na+ absorption across renal and intestinal epithelia. The apical Na+/H+ exchange activity is pharmacologically distinct from the basolateral Na+/H+ exchange activity, notably in terms of response to kinase regulation and in addition by the diuretic amiloride. NHE1 (SLC9A1), the first of these exchangers to be cloned, localizes by immunocytochemical studies only to the basolateral membranes of polarized epithelial cells. Transfection of OKP cells with dominant-negative PYK2 or small interfering PYK2 duplex RNA blocked acid activation of NHE3, whereas neither had an effect on glucocorticoid activation of NHE3. Dominant-negative PYK2 also blocked acid activation of SRC kinase , which is required for acid regulation of NHE3.