ArticleAnnals of neurology2009
Glutamate receptors on myelinated spinal cord axons: I. GluR6 kainate receptors.
Article in Annals of neurology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 107 citations in OpenAlex.
- Glutamate signaling and transport around nodes of Ranvier and internodal myelin regions.Histology and histopathology · 2026Review
- Potential physiological and pathological roles for axonal ryanodine receptors.Neural regeneration research · 2023Review
- An allergenic plant calmodulin fromFrontiers in immunology · 2022Article
- Neuron-Oligodendrocyte Interactions in the Structure and Integrity of Axons.Frontiers in cell and developmental biology · 2021Review
- IPNeurobiology of disease · 2020Article
- Inhibitory effects of fucoidan on NMDA receptors and l-type CaPharmaceutical biology · 2019Article
- Calcium Influx through Plasma-Membrane Nanoruptures Drives Axon Degeneration in a Model of Multiple Sclerosis.Neuron · 2019Article
- Regeneration of Spinal Cord Connectivity Through Stem Cell Transplantation and Biomaterial Scaffolds.Frontiers in cellular neuroscience · 2019Review
- The Influence of Glutamate on Axonal Compound Action Potential In Vitro.Journal of brachial plexus and peripheral nerve injury · 2016Article
- Imaging Axonal Degeneration and Repair in Preclinical Animal Models of Multiple Sclerosis.Frontiers in immunology · 2016Review
- Lactate transport and signaling in the brain: potential therapeutic targets and roles in body-brain interaction.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2015Review
- Neuroprotective effect of methylprednisolone combined with placenta-derived mesenchymal stem cell in rabbit model of spinal cord injury.International journal of clinical and experimental pathology · 2015Article
- The Role of Astrocytes in Multiple Sclerosis Progression.Frontiers in neurology · 2015Review
- Tyrosine phosphorylation of GluK2 up-regulates kainate receptor-mediated responses and downstream signaling after brain ischemia.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- In vivo evidence of glutamate toxicity in multiple sclerosis.Annals of neurology · 2014Article
- Relapsing and progressive forms of multiple sclerosis: insights from pathology.Current opinion in neurology · 2014Review
- Ionic regulation of cell volume changes and cell death after ischemic stroke.Translational stroke research · 2014Review
- Neurodegeneration in multiple sclerosis involves multiple pathogenic mechanisms.Degenerative neurological and neuromuscular disease · 2014Review
- Role of calpains in the injury-induced dysfunction and degeneration of the mammalian axon.Neurobiology of disease · 2013Review
- Ectopic vesicular glutamate release at the optic nerve head and axon loss in mouse experimental glaucoma.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
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10 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveThe deleterious effects of glutamate excitotoxicity are well described for central nervous system gray matter. Although overactivation of glutamate receptors also contributes to axonal injury, the mechanisms are poorly understood. Our goal was to elucidate the mechanisms of kainate receptor-dependent axonal Ca(2+) deregulation.
methodsDorsal column axons were loaded with a Ca(2+) indicator and imaged in vitro using confocal laser-scanning microscopy.
resultsActivation of glutamate receptor 6 (GluR6) kainate receptors promoted a substantial increase in axonal [Ca(2+)]. This Ca(2+) accumulation was due not only to influx from the extracellular space, but a significant component originated from ryanodine-dependent intracellular stores, which, in turn, depended on activation of L-type Ca(2+) channels: ryanodine, nimodipine, or nifedipine blocked the agonist-induced Ca(2+) increase. Also, GluR6 stimulation induced intraaxonal production of nitric oxide (NO), which greatly enhanced the Ca(2+) response: quenching of NO with intraaxonal (but not extracellular) scavengers, or inhibition of neuronal NO synthase with intraaxonal Nomega-nitro-L-arginine methyl ester, blocked the Ca(2+) increase. Loading axons with a peptide that mimics the C-terminal PDZ binding sequence of GluR6, thus interfering with the coupling of GluR6 to downstream effectors, greatly reduced the agonist-induced axonal Ca(2+) increase. Immunohistochemistry showed GluR6/7 clusters on the axolemma colocalized with neuronal NO synthase and Ca(v)1.2.
interpretationMyelinated spinal axons express functional GluR6-containing kainate receptors, forming part of novel signaling complexes reminiscent of postsynaptic membranes of glutamatergic synapses. The ability of such axonal "nanocomplexes" to release toxic amounts of Ca(2+) may represent a key mechanism of axonal degeneration in disorders such as multiple sclerosis where abnormal accumulation of glutamate and NO are known to occur.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.