ArticleJournal of neurophysiology2009
Glutamate transporters prevent excessive activation of NMDA receptors and extrasynaptic glutamate spillover in the spinal dorsal horn.
Article in Journal of neurophysiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 75 citations in OpenAlex.
- Targeting Spinal Dorsal Horn Sensitisation in Chronic Pain: Mechanisms and Translational Strategies.Neuroscience bulletin · 2026Review
- Functional and structural characterization of dendritic spine pathology in a mouse model of tauopathy.iScience · 2026Article
- Functional and structural characterization of dendritic spine pathology in a mouse model of tauopathy.bioRxiv : the preprint server for biology · 2026Article
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- Impact of electro-acupuncture on EAAT2 and NMDAR-2B expression in goats with visceral hypersensitivity.Heliyon · 2024Article
- Emerging Molecular and Synaptic Targets for the Management of Chronic Pain Caused by Systemic Lupus Erythematosus.International journal of molecular sciences · 2024Review
- Astrocyte β-Adrenergic Receptor Activity Regulates NMDA Receptor Signaling of Medial Prefrontal Cortex Pyramidal Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Real-time in vivo thoracic spinal glutamate sensing during myocardial ischemia.American journal of physiology. Heart and circulatory physiology · 2023Article
- Deficits in integrative NMDA receptors caused by Grin1 disruption can be rescued in adulthood.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Review
- Mechanisms of Transmission and Processing of Pain: A Narrative Review.International journal of environmental research and public health · 2023Review
- Calcium-Dependent Interplay of Lithium and Tricyclic Antidepressants, Amitriptyline and Desipramine, onInternational journal of molecular sciences · 2022Article
- Control of complex behavior by astrocytes and microglia.Neuroscience and biobehavioral reviews · 2022Review
- Article
- Sensitization of supra-threshold pain responses-Translational aspects and mechanisms.Frontiers in network physiology · 2022Review
- Leptin Contributes to Neuropathic Pain via Extrasynaptic NMDAR-nNOS Activation.Molecular neurobiology · 2021Article
- Role of Neuroimmune Crosstalk in Mediating the Anti-inflammatory and Analgesic Effects of Acupuncture on Inflammatory Pain.Frontiers in neuroscience · 2021Review
- Involvement of extrasynaptic glutamate in physiological and pathophysiological changes of neuronal excitability.Cellular and molecular life sciences : CMLS · 2018Review
- Dysregulation of sphingolipid metabolism contributes to bortezomib-induced neuropathic pain.The Journal of experimental medicine · 2018Article
- Cx43 and NMDA receptors changes in UL122 genetically modified mice hippocampus: a mechanism for spatial memory impairment.International journal of clinical and experimental pathology · 2018Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Activation of N-methyl-d-aspartate (NMDA) receptors in the spinal dorsal horn neurons is a key process related to sensory transmission, neural plasticity, and pathogenesis of pain. In this study, we investigated how activation of NMDA receptors in spinal substantia gelatinosa neurons is regulated by glutamate re-uptake through glutamate transporters located in the astrocytic and neuronal plasma membranes. Using visualized whole cell patch recording techniques, NMDA excitatory postsynaptic currents evoked by graded peripheral inputs in spinal substantia gelatinosa neurons of spinal slices from young adult rats were analyzed before and after combined inhibition of glial and neuronal glutamate transporters by d-threo-beta-benzyloxyaspartate (TBOA). Blockade of glutamate transporters increased the number and duration of NMDA receptors activated by weak and by strong primary afferent inputs as well as by exogenous glutamate. The enhancement in activation of NMDA receptors induced by TBOA was greater in neurons that have weaker synaptic input at baseline. Impaired glutamate uptake increased the open probability of NMDA channels and caused glutamate spillover outside the active synapses, leading to activation of extrasynaptic NMDA receptors and/or receptors located in neighboring synapses. Finally, blockade of glutamate transporters resulted in an increased proportion of NR2B subunit activation induced by peripheral input, and this increase was further augmented by stronger afferent input. These data indicate that glutamate transporters regulate spatiotemporal and intensity coding for sensory input and prevent excessive activation of glutamate receptors in the spinal dorsal horn. It is suggested that remedying dysfunctional glutamate transporters may be a potential new avenue to prevent the pathogenesis of pain.
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Registered trials
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