Decoupling the Na+–K+–ATPase in vivo: A possible new role in the gills of freshwater fishes

The literature suggests that when Na+–K+–ATPase has reduced access to its glycosphingolipid cofactor sulfogalactosyl ceramide (SGC), it is converted to a Na+ uniporter. We recently showed that such segregation can occur within a single membrane when Na+–K+–ATPase is excluded from membrane microdomains or ‘lipid rafts’ enriched in SGC (D. Lingwood, G. Harauz, J.S. Ballantyne, J. Biol. Chem. 280, 36545–36550). Specifically we demonstrated that Na+–K+–ATPase localizes to SGC-enriched rafts in the gill basolateral membrane (BLM) of rainbow trout exposed to seawater (SW) but not freshwater (FW). We therefore proposed that since the freshwater gill Na+–K+–ATPase was separated from BLM SGC it should also transport Na+ only, suggesting a new role for the pump in this epithelium. In this paper we discuss the biochemical evidence for SGC-based modulation of transport stoichiometry and highlight how a unique asparagine–lysine substitution in the FW pump isoform and FW gill transport energetics gear the Na+–K+–ATPase to perform Na+ uniport.