Glutamate uptake.
Brain tissue has a remarkable ability to accumulate glutamate. This ability is due to glutamate transporter proteins present in the plasma membranes of both glial cells and neurons. The transporter proteins represent the only (significant) mechanism for removal of glutamate from the extracellular fluid and their importance for the long-term maintenance of low and non-toxic concentrations of glutamate is now well documented. In addition to this simple, but essential glutamate removal role, the glutamate transporters appear to have more sophisticated functions in the modulation of neurotransmission. They may modify the time course of synaptic events, the extent and pattern of activation and desensitization of receptors outside the synaptic cleft and at neighboring synapses (intersynaptic cross-talk). Further, the glutamate transporters provide glutamate for synthesis of e.g. GABA, glutathione and protein, and for energy production. They also play roles in peripheral organs and tissues (e.g. bone, heart, intestine, kidneys, pancreas and placenta). Glutamate uptake appears to be modulated on virtually all possible levels, i.e. DNA transcription, mRNA splicing and degradation, protein synthesis and targeting, and actual amino acid transport activity and associated ion channel activities. A variety of soluble compounds (e.g. glutamate, cytokines and growth factors) influence glutamate transporter expression and activities. Neither the normal functioning of glutamatergic synapses nor the pathogenesis of major neurological diseases (e.g. cerebral ischemia, hypoglycemia, amyotrophic lateral sclerosis, Alzheimer's disease, traumatic brain injury, epilepsy and schizophrenia) as well as non-neurological diseases (e.g. osteoporosis) can be properly understood unless more is learned about these transporter proteins. Like glutamate itself, glutamate transporters are somehow involved in almost all aspects of normal and abnormal brain activity.
Danbolt
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Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1105, Blindern, N-0317, Oslo, Norway.
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D027322:Amino Acid Transport System X-AG; D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000378:metabolism; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D015640:Ion Channel Gating; D007473:Ion Channels / Q000378:metabolism; D017136:Ion Transport; D007511:Ischemia / Q000378:metabolism; D008297:Male; D008322:Mammals / Q000378:metabolism; D008630:Mercury Poisoning / Q000378:metabolism; D027501:Monocarboxylic Acid Transporters; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D009422:Nervous System Diseases / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D009928:Organ Specificity; D010920:Placenta / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011247:Pregnancy; D011487:Protein Conformation; D051381:Rats; D017470:Receptors, Glutamate / Q000737:chemistry / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014781:Viscera / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D000777:Anesthetics; D002352:Carrier Proteins; D007473:Ion Channels; D027501:Monocarboxylic Acid Transporters; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D017470:Receptors, Glutamate; D005973:Glutamine; D000431:Ethanol; D018698:Glutamic Acid; D012964:Sodium; D011188:Potassium