The glial cell glutamate uptake carrier countertransports pH-changing anions

Abstract

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.