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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

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