ArticlePloS one2015
A Metabotropic-Like Flux-Independent NMDA Receptor Regulates Ca2+ Exit from Endoplasmic Reticulum and Mitochondrial Membrane Potential in Cultured Astrocytes.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
23 citing papers in PubMed, 44 citations in OpenAlex.
- Calcium Signaling in Astrocytes and Its Role in the Central Nervous System Injury.Molecular neurobiology · 2025Review
- Kynurenic Acid Protects Against Myocardial Ischemia/Reperfusion Injury by Activating GPR35 Receptors and Preserving Mitochondrial Structure and Function.Biomolecules · 2025Article
- Mitochondrial fission process 1 protein: a comprehensive review of its core roles in mitochondrial dynamics, disease, and therapeutic targets.Frontiers in cell and developmental biology · 2025Review
- Two Signaling Modes Are Better than One: Flux-Independent Signaling by Ionotropic Glutamate Receptors Is Coming of Age.Biomedicines · 2024Review
- Cortical astrocyte N-methyl-D-aspartate receptors influence whisker barrel activity and sensory discrimination in mice.Nature communications · 2024Article
- Gene Expression at the Tripartite Synapse: Bridging the Gap Between Neurons and Astrocytes.Advances in neurobiology · 2024Review
- Astrocytes actively support long-range molecular clock synchronization of segregated neuronal populations.Scientific reports · 2023Article
- The Emerging Role of N-Methyl-D-Aspartate (NMDA) Receptors in the Cardiovascular System: Physiological Implications, Pathological Consequences, and Therapeutic Perspectives.International journal of molecular sciences · 2023Review
- Antibody induced seizure susceptibility and impaired cognitive performance in a passive transfer rat model of autoimmune encephalitis.Frontiers in immunology · 2023Article
- Intracellular CaFrontiers in physiology · 2023Review
- Targeting NMDA Receptors at the Neurovascular Unit: Past and Future Treatments for Central Nervous System Diseases.International journal of molecular sciences · 2022Review
- Ion flux-independent NMDA receptor signaling.Neuropharmacology · 2022Review
- Reversible Changes in BDNF Expression in MK-801-Induced Hippocampal Astrocytes Through NMDAR/PI3K/ERK Signaling.Frontiers in cellular neuroscience · 2021Article
- Tripartite signalling by NMDA receptors.Molecular brain · 2020Review
- NMDA Receptors in Astrocytes.Neurochemical research · 2020Review
- NMDA Receptors in Astrocytes: In Search for Roles in Neurotransmission and Astrocytic Homeostasis.International journal of molecular sciences · 2019Review
- Persistent Overexposure to N-Methyl-D-Aspartate (NMDA) Calcium-Dependently Downregulates Glutamine Synthetase, Aquaporin 4, and Kir4.1 Channel in Mouse Cortical Astrocytes.Neurotoxicity research · 2019Article
- The Role of NMDA Receptors in Alzheimer's Disease.Frontiers in neuroscience · 2019Review
- Flux-Independent NMDAR Signaling: Molecular Mediators, Cellular Functions, and Complexities.International journal of molecular sciences · 2018Review
- Article
Corrections and comments
- Erratum issued
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Astrocytes were long thought to be only structural cells in the CNS; however, their functional properties support their role in information processing and cognition. The ionotropic glutamate N-methyl D-aspartate (NMDA) receptor (NMDAR) is critical for CNS functions, but its expression and function in astrocytes is still a matter of research and debate. Here, we report immunofluorescence (IF) labeling in rat cultured cortical astrocytes (rCCA) of all NMDAR subunits, with phenotypes suggesting their intracellular transport, and their mRNA were detected by qRT-PCR. IF and Western Blot revealed GluN1 full-length synthesis, subunit critical for NMDAR assembly and transport, and its plasma membrane localization. Functionally, we found an iCa2+ rise after NMDA treatment in Fluo-4-AM labeled rCCA, an effect blocked by the NMDAR competitive inhibitors D(-)-2-amino-5-phosphonopentanoic acid (APV) and Kynurenic acid (KYNA) and dependent upon GluN1 expression as evidenced by siRNA knock down. Surprisingly, the iCa2+ rise was not blocked by MK-801, an NMDAR channel blocker, or by extracellular Ca2+ depletion, indicating flux-independent NMDAR function. In contrast, the IP3 receptor (IP3R) inhibitor XestosponginC did block this response, whereas a Ryanodine Receptor inhibitor did so only partially. Furthermore, tyrosine kinase inhibition with genistein enhanced the NMDA elicited iCa2+ rise to levels comparable to those reached by the gliotransmitter ATP, but with different population dynamics. Finally, NMDA depleted the rCCA mitochondrial membrane potential (mΔψ) measured with JC-1. Our results demonstrate that rCCA express NMDAR subunits which assemble into functional receptors that mediate a metabotropic-like, non-canonical, flux-independent iCa2+ increase.
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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.