Inhibition of lactate export by quercetin acidifies rat glial cells in vitro

The relationship between glial lactate release and glial intracellular pH (pH_i) regulation is studied using C6 glioma cells and rat astrocytes in vitro, and the lactate transport inhibitors quercetin and α-cyano-4-hydroxycinnamate (CHC). pH_i is measured using 2′,7′-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF). The results show that lactate release is mediated partly by a specific lactate transport system inhibitable by quercetin (50 μM), but not by CHC (5 mM). Inhibition by quercetin results in a significant 3–4-fold increase of intracellular lactate and a decrease of intracellular pH to 6.9. A participation of quercetin-inhibitable lactate transport in glial pH_i-regulation is suggested by the observation that pH_i-homeostasis after acidification by diffusion of undissociated lactic acid into the cell is inhibited by quercetin. The existence of a system controlling lactate release in glial cells may also reflect a function of astrocytes to supply neurons with lactate.