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 HCO3-) are transported out. This stoichiometry predicts a minimum [Glu]o of 0.6 muM normally (tonically activating presynaptic autoreceptors and postsynaptic NMDA receptors), and 370 muM during brain anoxia (high enough to kill neurons). Transport of OH-/HCO3- on the uptake carrier generates significant pH changes, and may provide a mechanism for neuron-glial interaction.