Functional integration of the transport of ammonium, glutamate and glutamine in astrocytes

This short review surveys the effects of extracellular potassium, released by neuronal activity, on the fluxes of ammonium, glutamate and glutamine in astrocytes. There is evidence that each of these fluxes is modulated by po tassium-induced changes in astrocytic pH. The result is viewed as an integr ated response to neuronal activity. The unusually high permeability of astrocyte cell membrane to ammonium ions , together with the normal transmembrane gradient of pH, enables astrocytes to accumulate ammonium appreciably. However, at loci of neuronal activity, effective ammonium ion permeability is diminished and the cytosol is alkal inized, resulting in a local decline in intracellular ammonium concentratio n. Intracellular potassium concentration rises at these same loci, creating the conditions for a 'potassium-ammonium countercurrent' in which ammonium ions migrate intracellularly towards sites of neuronal activity as potassi um ions diffuse away. Physiologic elevations of extracellular potassium evoke a marked 'paradoxic al' increase in the velocity of glutamate uptake in astrocytes. This increa se correlates well with the extent of potassium-induced alkalinization. Fur ther, recent evidence identifies a major transporter of glutamine in astroc ytes (System N) as a glutamine/proton exchanger. Potassium can reverse the transmembrane gradient of protons in astrocytes, and increase intracellular glutamine concentration, creating the conditions for a reversal of glutami ne flux via System N from uptake to export. These flux changes, evoked by p otassium released from active neurons, combine to accelerate glutamate-glut amine cycling. (C) 2000 Elsevier Science Ltd. All rights reserved.