Na+-inhibitory sites of the Na+/H+ exchanger are Li+ substrate sites

Department of Biology, Syracuse University, Syracuse, New York Submitted 12 November 2004 ; accepted in final form 14 March 2005 Amiloride-inhibitable Li + influx in dog red blood cells is mediated by the Na + /H + exchanger, NHE. However, there are substantial differences between the properties of Li + transport and Na + transport through the NHE. Li + influx is activated by cell shrinkage, and Na + influx is not, as we reported previously (Dunham PB, Kelley SJ, and Logue PJ. Am J Physiol Cell Physiol 287: C336–C344, 2004). Li + influx is a sigmoidal function of its concentration, and Na + activation is linear at low Na + concentrations. Li + does not inhibit its own influx; in contrast, Na + inhibits Na + influx. Li + prevents this inhibition by Na + . Na + is a mixed or noncompetitive inhibitor of Li + influx, implying that both a Na + and a Li + can be bound at the same time. In contrast, Li + is a competitive inhibitor of Na + influx, suggesting Li + binding at one class of sites on the transporter. Because the properties of Li + transport and Na + transport are different, a simple explanation is that Na + and Li + are transported by separate sites. The similarities of the properties of Li + transport and the inhibition of Na + transport by Na + suggest that Li + is transported by the Na + -inhibitory sites. Li + /H + exchange; amiloride; Na + substrate sites Address for reprint requests and other correspondence: P. B. Dunham, Biological Research Laboratories, Syracuse University, 130 College Place, Syracuse, NY 13244-1220 (e-mail: pbdunham{at}syr.edu )