Astrocyte glutamate transport: Review of properties, regulation, and physiological functions

Abstract

Rapid removal of glutamate from the extracellular space is required for the survival and normal function of neurons. Although glutamate transporters are expressed by all CNS cell types, astrocytes are the cell type primarily responsible for glutamate uptake. Astrocyte glutamate uptake also plays a role in regulating the activity of glutamatergic synapses. Lastly, release of glutamate from astrocytes, via transporter reversal and other routes, can contribute to glutamate receptor activation. This review examines the mechanisms of astrocyte glutamate uptake and release, with particular focus on high-affinity Na(+)-dependent transporters. Transporter regulation, energetics, and physiological roles are discussed.

Attenuation of neurological injury with early baicalein treatment following subarachnoid hemorrhage in rats

“…12 In addition, increased glutamate levels may lead to astrocyte dysfunction or apoptosis and decreased astrocyte activity might decrease glutamate uptake and enhance neuronal death. 1,22,23,25,32 As previously reported, 29 CVS is a major cause of mortality and morbidity; in the present study, we further demonstrated that the CVS was positively correlated with neuronal degeneration on Day 7 after SAH. At the same time, we found significant correlations among GLT-1, MDA, SOD, and catalase after SAH.…”

Attenuation of neurological injury with early baicalein treatment following subarachnoid hemorrhage in rats

“…12 In addition, increased glutamate levels may lead to astrocyte dysfunction or apoptosis and decreased astrocyte activity might decrease glutamate uptake and enhance neuronal death. 1,22,23,25,32 As previously reported, 29 CVS is a major cause of mortality and morbidity; in the present study, we further demonstrated that the CVS was positively correlated with neuronal degeneration on Day 7 after SAH. At the same time, we found significant correlations among GLT-1, MDA, SOD, and catalase after SAH.…”

Use of Randomized Submaximal Glutamate Stimulus to Interpret Glial Effects on Neuronal Calcium Dynamics

“…As expected, cultures low in glia on average demonstrated higher amplitude neuronal [Ca 2+ ] i response to GLU addition since it is well known that glia (astrocytes) take up glutamate [6] and cultures low in glia are injured to a greater extent by glutamate than cultures high in glia [14]. We had previously shown that for a single glutamate stimulus in the micromolar range, that increasing concentrations of glutamate resulted in greater AUC as expressed as a slower (or lack of) recovery to baseline [Ca 2+ ] i [2].…”

Segregated Expression of AMPA-Type Glutamate Receptors and Glutamate Transporters Defines Distinct Astrocyte Populations in the Mouse Hippocampus

“…The properties of the GluT cells are in line with the classical view of protoplasmic astrocytes as a sink for synaptically released glutamate (Anderson and Swanson, 2000). Obviously, the GluR cells serve other functions.…”

Attenuation of neurological injury with early baicalein treatment following subarachnoid hemorrhage in rats

“…12 In addition, increased glutamate levels may lead to astrocyte dysfunction or apoptosis and decreased astrocyte activity might decrease glutamate uptake and enhance neuronal death. 1,22,23,25,32 As previously reported, 29 CVS is a major cause of mortality and morbidity; in the present study, we further demonstrated that the CVS was positively correlated with neuronal degeneration on Day 7 after SAH. At the same time, we found significant correlations among GLT-1, MDA, SOD, and catalase after SAH.…”

Use of Randomized Submaximal Glutamate Stimulus to Interpret Glial Effects on Neuronal Calcium Dynamics

“…As expected, cultures low in glia on average demonstrated higher amplitude neuronal [Ca 2+ ] i response to GLU addition since it is well known that glia (astrocytes) take up glutamate [6] and cultures low in glia are injured to a greater extent by glutamate than cultures high in glia [14]. We had previously shown that for a single glutamate stimulus in the micromolar range, that increasing concentrations of glutamate resulted in greater AUC as expressed as a slower (or lack of) recovery to baseline [Ca 2+ ] i [2].…”

Segregated Expression of AMPA-Type Glutamate Receptors and Glutamate Transporters Defines Distinct Astrocyte Populations in the Mouse Hippocampus

“…The properties of the GluT cells are in line with the classical view of protoplasmic astrocytes as a sink for synaptically released glutamate (Anderson and Swanson, 2000). Obviously, the GluR cells serve other functions.…”

Attenuation of neurological injury with early baicalein treatment following subarachnoid hemorrhage in rats

“…12 In addition, increased glutamate levels may lead to astrocyte dysfunction or apoptosis and decreased astrocyte activity might decrease glutamate uptake and enhance neuronal death. 1,22,23,25,32 As previously reported, 29 CVS is a major cause of mortality and morbidity; in the present study, we further demonstrated that the CVS was positively correlated with neuronal degeneration on Day 7 after SAH. At the same time, we found significant correlations among GLT-1, MDA, SOD, and catalase after SAH.…”

Use of Randomized Submaximal Glutamate Stimulus to Interpret Glial Effects on Neuronal Calcium Dynamics

“…As expected, cultures low in glia on average demonstrated higher amplitude neuronal [Ca 2+ ] i response to GLU addition since it is well known that glia (astrocytes) take up glutamate [6] and cultures low in glia are injured to a greater extent by glutamate than cultures high in glia [14]. We had previously shown that for a single glutamate stimulus in the micromolar range, that increasing concentrations of glutamate resulted in greater AUC as expressed as a slower (or lack of) recovery to baseline [Ca 2+ ] i [2].…”

Segregated Expression of AMPA-Type Glutamate Receptors and Glutamate Transporters Defines Distinct Astrocyte Populations in the Mouse Hippocampus

“…The properties of the GluT cells are in line with the classical view of protoplasmic astrocytes as a sink for synaptically released glutamate (Anderson and Swanson, 2000). Obviously, the GluR cells serve other functions.…”