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 potassium-induced changes in astrocytic pH. The result is viewed as an integrated 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 alkalinized, resulting in a local decline in intracellular ammonium concentration. 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 potassium ions diffuse away. Physiologic elevations of extracellular potassium evoke a marked 'paradoxical' increase in the velocity of glutamate uptake in astrocytes. This increase correlates well with the extent of potassium-induced alkalinization. Further, recent evidence identifies a major transporter of glutamine in astrocytes (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 glutamine flux via System N from uptake to export. These flux changes, evoked by potassium released from active neurons, combine to accelerate glutamate-glutamine cycling.
Brookes
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Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore 21201, USA. nbrookes@umaryland.edu
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D000644:Quaternary Ammonium Compounds / Q000378:metabolism*
D000644:Quaternary Ammonium Compounds; D005973:Glutamine; D018698:Glutamic Acid