EXPRESSION OF THE HUMAN SODIUM-PROTON EXCHANGER NHE-1 IN XENOPUS-LAEVIS OOCYTES ENHANCES SODIUM-PROTON EXCHANGE ACTIVITY AND ESTABLISHES SODIUM-LITHIUM COUNTERTRANSPORT

We investigated whether the human sodium/proton (Na+/H+) exchanger isoform 1 (NHE-1) can mediate sodium/lithium (Na+/Li+) countertransport. Using the Xenopus laevis oocyte expression system we determined amiloride-sensitive Lif uptake, a measure of Na+/H+ exchange, in oocytes injected with water or NHE-1 cRNA. Amiloride-sensitive Li+ uptake was three- to tenfold enhanced over control in NHE-1 cRNA-injected cells and was selectively inhibited by 0.01 mu M HOE 694 [i.e. (3-methylsulphonyl-4-piperidinobenzoyl) guanidine methanesulphonate]. The endogenously present Na+/H+ exchanger was insensitive to HOE 694. After acidification of oocytes from pH 7.7 to 6.8, amiloride-sensitive Li+ uptake was four- to tenfold higher in NHE-1 cRNA-injected cells than in controls. Li+ efflux from control oocytes was independent of extracellular Na+, indicating that these cells expressed no measurable Na+/Li+ countertransport activity. In NHE-1 cRNA-injected oocytes, Li+ efflux was distinctly enhanced by extracellular Na+ ions. This Na+-dependent Li+ efflux was inhibited by ethylisopropylamiloride, phloretin and by cytosolic acidification. The data show that expression of the NHE-1 in X. laevis oocytes induces the expression of Na+/Li+ countertransport. The data confirm that Na+/H+ exchange and Na+/Li+ countertransport are mediated by the same transport system.