The glutamine transporter SNAT3 (SLC38A3) is involved in the glutamine efflux from brain astrocytes during the glutamate/glutamine cycle (Deitmer, Bröer & Bröer, 2003, J. Neurochem. 87). SNAT3 is an acid/base-coupled transporter with a stoichiometry of 1 glutamine and 1 Na+ in antiport with 1 H+. We have studied, if the sodium/bicarbonate cotransporter (NBCe1), which increases the cytosolic buffer capacity by shuttling bicarbonate across the cell membrane (Becker & Deitmer, 2004, J. Biol. Chem. 279), may enhance SNAT3 transport activity. We co-expressed SNAT3 and NBCe1 in Xenopus oocytes and measured membrane current and pH with two-electrode voltage-clamp and pH-sensitive microelectrodes, and also measured radio-labelled glutamine fluxes. The presence of NBCe1 reduced the uptake of glutamine into the oocytes, but increased the efflux. In cultured rat astrocytes we observed a decreased efflux of glutamine, when the NBCe1 was inhibited by DIDS. Our results suggest that NBCe1 modulates glutamine flux via SNAT3 differentially; in glial cells, where both NBCe1 and SNAT3 are present, this mechanism would increase the efflux, but hinder the (re-)uptake, of glutamine.

Supported by the DFG (De 231/16; GRK 845).