Independence of dimethylamiloride-sensitive Li+ efflux pathways and Na+-Li+ countertransport in human erythrocytes.

The in vivo function of the erythrocyte Na+-Li+ countertransport (SLC) is unknown. Whether SLC may reflect an operational mode of the widespread Na+-H+ exchanger (NHE) or may otherwise be expression of an independent membrane transport, remains presently unclear. We explored the presence of 5-(N,N-dimethyl)-amiloride (DMA)-sensitive Li+ pathways in human erythrocytes where the activity of the Na+ pump, Na+-K+ cotransport and anion exchange were suitably inhibited. A total of 0.02 mM DMA had no effect on SLC as expected, but gave a significant inhibition of Li+ efflux into both Na+ and Na+-free media. This DMA-sensitive Li+ pathway, but not SLC, was significantly enhanced by hyperosmolar cell shrinkage, which is a characteristic feature of NHE. In conclusion, DMA-sensitive Li+ pathways, possibly mediated by NHE, are present in erythrocytes and coexist with the DMA-insensitive, SLC. This finding supports the notion that SLC is independent of amiloride-sensitive NHE.