The electrogenic Na+–HCO3- cotransporter NBCe1-B is regulated by intracellular Mg2+

NBCe1-B, a major splice variant of the electrogenic Na+–HCO3- cotransporter (NBCe1) fulfills basic cellular functions including regulation of intracellular pH and epithelial HCO3- secretion. However, its cellular regulatory mechanism still remains elusive. Here, we provide evidence for the first time that NBCe1-B activity can be controlled by intracellular Mg2+ (Mg2+i), the physiologically most abundant intracellular divalent cation. Using the whole-cell patch–clamp technique, we found that recombinant NBCe1-B currents expressed in HEK293 and NIH3T3 cells were inhibited voltage-independently by Mg2+i in a concentration-dependent manner (Ki ≈ 0.01 mM). The Mg2+i inhibition was partially relieved by truncation of the NBCe1-B specific N-terminal region (Ki ≈ 0.3 mM), and was also observed for native electrogenic Na+–HCO3- cotransporter current in bovine parotid acinar cells that endogenously express NBCe1-B (Ki ≈ 1 mM). These results suggest that Mg2+ may be a cytosolic factor that limits intrinsic cotransport activity of NBCe1-B in mammalian cells.