ArticleThe Journal of biological chemistry2013
Loss of calcium/calmodulin-dependent protein kinase II activity in cortical astrocytes decreases glutamate uptake and induces neurotoxic release of ATP.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- Calcium Buffering in Astrocytes and Its Relevance for Experimental Data Interpretation and Computational Modeling.Journal of neurochemistry · 2026Review
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- Glutamate, a Key for Astrocytes to Participate in Brain Function and Diseases.Neurochemical research · 2025Review
- DYRK1A in the physiology and pathology of the neuron-astrocyte axis.Frontiers in neuroscience · 2025Review
- Cells and Molecules Underpinning Cannabis-Related Variations in Cortical Thickness during Adolescence.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Cx43 hemichannels and panx1 channels contribute to ethanol-induced astrocyte dysfunction and damage.Biological research · 2024Article
- [PI3K/Akt/Erk signaling pathway mediates neuroprotection of CaMKⅡγ and CaMKⅡδ against ischemic reperfusion injury in mice].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- The GHB analogue HOCPCA improves deficits in cognition and sensorimotor function after MCAO via CaMKIIα.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Role of glia and extracellular matrix in controlling neuroplasticity in the central nervous system.Seminars in immunopathology · 2023Review
- Proposed mechanisms of tau: relationships to traumatic brain injury, Alzheimer's disease, and epilepsy.Frontiers in neurology · 2023Article
- Applications of Induced Pluripotent Stem Cell-Derived Glia in Brain Disease Research and Treatment.Handbook of experimental pharmacology · 2023Review
- Role of CaFrontiers in molecular neuroscience · 2022Review
- Rapid Regulation of Glutamate Transport: Where Do We Go from Here?Neurochemical research · 2022Review
- Calcium/Calmodulin-Dependent Protein Kinase II in Cerebrovascular Diseases.Translational stroke research · 2021Review
- Memantine and Ibuprofen pretreatment exerts anti-inflammatory effect against streptozotocin-induced astroglial inflammation via modulation of NMDA receptor-associated downstream calcium ion signaling.Inflammopharmacology · 2021Article
- CaMKII enhances voltage-gated sodium channel Nav1.6 activity and neuronal excitability.The Journal of biological chemistry · 2020Article
- Butanol Extract of Tinospora cordifolia Ameliorates Cognitive Deficits Associated with Glutamate-Induced Excitotoxicity: A Mechanistic Study Using Hippocampal Neurons.Neuromolecular medicine · 2020Article
- Loss of insulin-like growth factor-1 signaling in astrocytes disrupts glutamate handling.Journal of neurochemistry · 2019Article
- Zika Virus Infection Disrupts Astrocytic Proteins Involved in Synapse Control and Axon Guidance.Frontiers in microbiology · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The extent of calcium/calmodulin-dependent protein kinase II (CaMKII) inactivation in the brain after ischemia correlates with the extent of damage. We have previously shown that a loss of CaMKII activity in neurons is detrimental to neuronal viability by inducing excitotoxic glutamate release. In the current study we extend these findings to show that the ability of astrocytes to buffer extracellular glutamate is reduced when CaMKII is inhibited. Furthermore, CaMKII inhibition in astrocytes is associated with the rapid onset of intracellular calcium oscillations. Surprisingly, this rapid calcium influx is blocked by the N-type calcium channel antagonist, ω-conotoxin. Although the function of N-type calcium channels within astrocytes is controversial, these voltage-gated calcium channels have been linked to calcium-dependent vesicular gliotransmitter release. When extracellular glutamate and ATP levels are measured after CaMKII inhibition within our enriched astrocyte cultures, no alterations in glutamate levels are observed, whereas ATP levels in the extracellular environment significantly increase. Extracellular ATP accumulation associated with CaMKII inhibition contributes both to calcium oscillations within astrocytes and ultimately cortical neuron toxicity. Thus, a loss of CaMKII signaling within astrocytes dysregulates glutamate uptake and supports ATP release, two processes that would compromise neuronal survival after ischemic/excitotoxic insults.
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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.