Identification and properties of a novel variant of NBC4 (Na ⁺/HCO₃^- co-transporter 4) that is predominantly expressed in the choroid plexus

Secretion of HCO₃^- at the apical side of the epithelial cells of the choroid plexus is an essential step in the formation of cerebrospinal fluid. Anion conductance with a high degree of HCO ₃^- permeability has been observed and suggested to be the major pathway for HCO₃^- transport across the apical membrane. Recently, it was found that NBC (Na⁺/HCO₃ ^- co-transporter) 4, an electrogenic member of the NBC family, was expressed in the choroid plexus. We found that a novel variant of the NBC4 [NBC4g/Slc4a5 (solute carrier family 4, sodium bicarbonate cotransporter, member 5)] is almost exclusively expressed in the apical membrane of rat choroid plexus epithelium at exceptionally high levels. RNA interference-mediated knockdown allowed the functional demonstration that NBC4g is the major player in the HCO₃^- transport across the apical membrane of the choroid plexus epithelium. When combined with a recent observation that in choroid plexus epithelial cells electrogenic NBC operates with a stoichiometry of 3:1, the results of the present study suggest that NBC4g mediates the efflux of HCO₃^- and contributes to cerebrospinal fluid production.