The glial cell glutamate uptake carrier countertransports pH-changing anions

UPTAKE into glial cells helps to terminate glutamate's neurotransmitter action and to keep its extracellular concentration, [Glu]o, below neurotoxic levels. The accumulative power of the uptake carrier stems from its transport of inorganic ions such as sodium (into the cell) and potassium (out of the cell)1–3. There is controversy over whether the carrier also transports a proton (or pH-changing anion)4,5. Here we show that the carrier generates an alkalinization outside and an acidification inside glial cells, and transports anions out of the cells, suggesting that there is a carrier cycle in which two Na+ accompany each glutamate anion into the cell, while one K+ and one OH−(or HCO−3) are transported out. This stoichiometry predicts a minimum [Glu]o of 0.6 μM normally (tonically activating presynaptic autoreceptors and postsynaptic NMD A receptors), and 370 μM during brain anoxia (high enough to kill neurons). Transport of OH−/HCO−3 on the uptake carrier generates significant pH changes, and may provide a mechanism for neuron–glial interaction.