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The Journal of Neuroscience, June 15, 1998, 18(12):4490-4499
Neuronal Expression of the Glutamate Transporter GLT-1 in Hippocampal Microcultures
Steven Mennerick1, Rupali P. Dhond1, Ann Benz1, Wanyan Xu1, Jeffrey D. Rothstein2, Niels C. Danbolt3, Keith E. Isenberg1, and Charles F. Zorumski1 1 Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, 2 Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, and 3 Anatomical Institute, University of Oslo, Oslo, Norway
To address the question of the relative contributions of glial and neuronal glutamate transport in the vertebrate CNS, we studied the distribution of forebrain glutamate transporters in rat hippocampal microcultures, a preparation in which physiological functions of glutamate transporters have been well characterized. Two of the three transporters, GLAST (EAAT1) and EAAC1 (EAAT3), are localized to microculture glia and neurons, respectively, as expected. However, we find strong immunoreactivity for the third glutamate transporter GLT-1 (EAAT2), a putatively glial transporter, in microculture neurons and in a small subset of microculture glia. Indistinguishable immunohistochemical staining patterns for GLT-1 were obtained with antibodies directed against both the N terminal and C terminal of the GLT-1 protein. Double-labeling experiments suggest that neuronal GLT-1 protein is primarily localized to the dendrites of excitatory neurons. Neuronal electrogenic transport currents in response to D-aspartate applications were occluded by the selective GLT-1 inhibitor dihydrokainate. In contrast, glia exhibited a larger transporter current density than did neurons, and the glial transport current was less sensitive to dihydrokainate. Neuronal transport currents were potentiated less than were glial currents when the chaotropic anion thiocyanate was substituted for gluconate in the whole-cell recording pipette, consistent with the previously reported lower anion permeability of EAAC1 and GLT-1 compared with that of GLAST. After microculture glia were rendered nonviable, excitatory autaptic currents (EACs) were prolonged in the presence of dihydrokainate, suggesting that neuronal GLT-1 is capable of participating in the clearance of synaptically released glutamate. Our results suggest that the initially proposed characterization of GLT-1 as a purely glial transporter is too simplistic and that under certain conditions functional GLT-1 protein can be expressed in brain neurons. The study suggests that changes in GLT-1 levels that occur with pathology or experimental manipulations cannot be assumed to be glial.
Key words: glutamate transport; glutamate uptake; astrocyte; postsynaptic; dendrite; microculture; hippocampus
Copyright © 1998 Society for Neuroscience 0270-6474/98/18124490-10$05.00/0
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