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Science 13 June 1997:
Vol. 276. no. 5319, pp. 1699 - 1702
DOI: 10.1126/science.276.5319.1699
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Reports

Epilepsy and Exacerbation of Brain Injury in Mice Lacking the Glutamate Transporter GLT-1

Kohichi Tanaka, * Kei Watase, Toshiya Manabe, Keiko Yamada, Masahiko Watanabe, Katsunobu Takahashi, Hisayuki Iwama, Toru Nishikawa, Nobutsune Ichihara, Tateki Kikuchi, Shigeru Okuyama, Naoya Kawashima, Seiji Hori, Misato Takimoto, Keiji Wada

Extracellular levels of the excitatory neurotransmitter glutamate in the nervous system are maintained by transporters that actively remove glutamate from the extracellular space. Homozygous mice deficient in GLT-1, a widely distributed astrocytic glutamate transporter, show lethal spontaneous seizures and increased susceptibility to acute cortical injury. These effects can be attributed to elevated levels of residual glutamate in the brains of these mice.

K. Tanaka, K. Watase, K. Wada, Department of Degenerative Neurological Diseases, National Institute of Neuroscience, Kodaira, Tokyo 187, Japan.
T. Manabe, Department of Neurophysiology, Faculty of Medicine, University of Tokyo, Tokyo 113 Japan.
K. Yamada and M. Watanabe, Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060, Japan.
K. Takahashi, H. Iwama, T. Nishikawa, Department of Mental Disorder Research, National Institute of Neuroscience, Kodaira, Tokyo 187, Japan.
N. Ichihara and T. Kikuchi, Department of Animal Models for Human Disease, National Institute of Neuroscience, Kodaira, Tokyo 187, Japan.
S. Okuyama and N. Kawashima, 1st Laboratory, Medicinal Research Laboratories, Taisho Pharmaceutical Co., 1-403 Yoshino-cho, Ohmiya-shi, Saitama 330, Japan.
S. Hori and M. Takimoto, International Research Laboratories, Ciba-Geigy Japan, 10-66, Miyuki-cho, Takarazuka 665, Japan.
*   To whom correspondence should be addressed. E-mail: tanaka{at}ncnaxp.ncnp.go.jp

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Differentiation of Substrate and Nonsubstrate Inhibitors of the High-Affinity, Sodium-Dependent Glutamate Transporters.
H. P. Koch, M. P. Kavanaugh, C. S. Esslinger, N. Zerangue, J. M. Humphrey, S. G. Amara, A. R. Chamberlin, and R. J. Bridges (1999)
Mol. Pharmacol. 56, 1095-1104
   Abstract »    Full Text »
The Effects of Hypothermia on a Cloned Human Brain Glutamate Transporter (hGLT-1) Expressed in Chinese Hamster Ovary Cells: -[3H]L-Glutamate Uptake Study.
F. Sakai and K. Amaha (1999)
Anesth. Analg. 89, 1546
   Abstract »    Full Text »    PDF »
Glutamate Transporters Contribute to the Time Course of Synaptic Transmission in Cerebellar Granule Cells.
L. S. Overstreet, G. A. Kinney, Y.-B. Liu, D. Billups, and N. T. Slater (1999)
J. Neurosci. 19, 9663-9673
   Abstract »    Full Text »    PDF »
Glutamate transporters in kidney and brain.
M. A. Hediger (1999)
Am J Physiol Renal Physiol 277, F487-F492
   Abstract »    Full Text »    PDF »
Neurotransmitter Transporters in the Central Nervous System.
J. Masson, C. Sagne, M. Hamon, and S. E. Mestikawy (1999)
Pharmacol. Rev. 51, 439-464
   Abstract »    Full Text »    PDF »
Three-Dimensional Relationships between Hippocampal Synapses and Astrocytes.
R. Ventura and K. M. Harris (1999)
J. Neurosci. 19, 6897-6906
   Abstract »    Full Text »    PDF »
Seizure-Induced Cell Death Produced by Repeated Tetanic Stimulation In Vitro: Possible Role of Endoplasmic Reticulum Calcium Stores.
M. R. Pelletier, J. S. Wadia, L. R. Mills, and P. L. Carlen (1999)
J Neurophysiol 81, 3054-3064
   Abstract »    Full Text »    PDF »
Structural Features of the Glutamate Transporter Family.
D. J. Slotboom, W. N. Konings, and J. S. Lolkema (1999)
Microbiol. Mol. Biol. Rev. 63, 293-307
   Abstract »    Full Text »    PDF »
Expression of the GLT-1 Subtype of Na+-Dependent Glutamate Transporter: Pharmacological Characterization and Lack of Regulation by Protein Kinase C.
J. Tan, O. Zelenaia, D. Correale, J. D. Rothstein, and M. B. Robinson (1999)
J. Pharmacol. Exp. Ther. 289, 1600-1610
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Nontransportable Inhibitors Attenuate Reversal of Glutamate Uptake in Synaptosomes Following a Metabolic Insult.
H. P. Koch, A. R. Chamberlin, and R. J. Bridges (1999)
Mol. Pharmacol. 55, 1044-1048
   Abstract »    Full Text »
Optical Detection of Synaptically Induced Glutamate Transport in Hippocampal Slices.
S. Kojima, T. Nakamura, T. Nidaira, K. Nakamura, N. Ooashi, E. Ito, K. Watase, K. Tanaka, K. Wada, Y. Kudo, et al. (1999)
J. Neurosci. 19, 2580-2588
   Abstract »    Full Text »    PDF »
Two serine residues of the glutamate transporter GLT-1 are crucial for coupling the fluxes of sodium and the neurotransmitter.
Y. Zhang and B. I. Kanner (1999)
PNAS 96, 1710-1715
   Abstract »    Full Text »    PDF »
The Number of Glutamate Transporter Subtype Molecules at Glutamatergic Synapses: Chemical and Stereological Quantification in Young Adult Rat Brain.
K. P. Lehre and N. C. Danbolt (1998)
J. Neurosci. 18, 8751-8757
   Abstract »    Full Text »    PDF »
Molecular Biology of Mammalian Plasma Membrane Amino Acid Transporters.
M. PALACIN, R. ESTEVEZ, J. BERTRAN, and A. ZORZANO (1998)
Physiol Rev 78, 969-1054
   Abstract »    Full Text »    PDF »
Glial Contribution to Glutamate Uptake at Schaffer Collateral-Commissural Synapses in the Hippocampus.
D. E. Bergles and C. E. Jahr (1998)
J. Neurosci. 18, 7709-7716
   Abstract »    Full Text »    PDF »
The Caenorhabditis elegans Gene T23G5.5 Encodes an Antidepressant- and Cocaine-Sensitive Dopamine Transporter.
L. D. Jayanthi, S. Apparsundaram, M. D. Malone, E. Ward, D. M. Miller, M. Eppler, and R. D. Blakely (1998)
Mol. Pharmacol. 54, 601-609
   Abstract »    Full Text »


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