ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Metabolic autocrine regulation of neurons involves cooperation among pannexin hemichannels, adenosine receptors, and KATP channels.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.
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Who cites it
110 citing papers in PubMed, 175 citations in OpenAlex.
- Panx1a modulates metabolic stress signaling and synaptic composition in the developing zebrafish brain.Cell and tissue research · 2025Article
- WONOEP XVII appraisal: Targeting network excitability beyond the synapse -Neurotransmitter, ionic, and electro -diffusions.Epilepsia · 2025Review
- Exogenous Ketone Supplementation Enhances the Anti-Epileptic Effect of Levetiracetam in Wistar Albino Glaxo/Rijswijk Rats.Nutrients · 2025Article
- Adenosine Kinase: An Epigenetic Modulator and Drug Target.Journal of inherited metabolic disease · 2025Review
- A ketogenic diet decreases sevoflurane-induced burst suppression in rats.Brain research bulletin · 2025Article
- Regulation of GABAergic neurotransmission by purinergic receptors in brain physiology and disease.Purinergic signalling · 2025Review
- Impact of the Ketogenic Diet on Neurological Diseases: A Review.Life (Basel, Switzerland) · 2025Review
- Acetoacetate, a ketone body, attenuates neuronal bursts in acutely-induced epileptiform slices of the mouse hippocampus.Frontiers in cellular neuroscience · 2025Article
- Ketogenic diet, adenosine, and dopamine in addiction and psychiatry.Frontiers in nutrition · 2025Review
- Neuroglia and brain energy metabolism.Handbook of clinical neurology · 2025Review
- Putative Role of Adenosine A1 Receptors in Exogenous Ketone Supplements-Evoked Anti-Epileptic Effect.International journal of molecular sciences · 2024Review
- Inhibition of astroglial hemichannels prevents synaptic transmission decline during spreading depression.Biological research · 2024Article
- Exogenous Ketone Supplement Administration Abrogated Isoflurane-Anesthesia-Induced Increase in Blood Glucose Level in Female WAG/Rij Rats.Nutrients · 2024Article
- Adenosine APurinergic signalling · 2023Article
- Dose-Dependent Beneficial Effect of Ketone Supplement-Evoked Ketosis on Anxiety Level in Female WAG/Rij Rats: Sometimes Less Is More.Nutrients · 2023Article
- Emerging Nonpharmacologic Interventions to Treat Diabetic Peripheral Neuropathy.Antioxidants & redox signaling · 2023Review
- Ketogenic Diet and Ketone Bodies against Ischemic Injury: Targets, Mechanisms, and Therapeutic Potential.International journal of molecular sciences · 2023Review
- Extracellular ATP/adenosine dynamics in the brain and its role in health and disease.Frontiers in cell and developmental biology · 2023Review
- Pannexin 1 activity in astroglia sets hippocampal neuronal network patterns.PLoS biology · 2022Article
- The Metabolic Role of Ketogenic Diets in Treating Epilepsy.Nutrients · 2022Review
50 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Metabolic perturbations that decrease or limit blood glucose-such as fasting or adhering to a ketogenic diet-reduce epileptic seizures significantly. To date, the critical links between altered metabolism and decreased neuronal activity remain unknown. More generally, metabolic changes accompany numerous CNS disorders, and the purines ATP and its core molecule adenosine are poised to translate cell energy into altered neuronal activity. Here we show that nonpathological changes in metabolism induce a purinergic autoregulation of hippocampal CA3 pyramidal neuron excitability. During conditions of sufficient intracellular ATP, reducing extracellular glucose induces pannexin-1 hemichannel-mediated ATP release directly from CA3 neurons. This extracellular ATP is dephosphorylated to adenosine, activates neuronal adenosine A(1) receptors, and, unexpectedly, hyperpolarizes neuronal membrane potential via ATP-sensitive K(+) channels. Together, these data delineate an autocrine regulation of neuronal excitability via ATP and adenosine in a seizure-prone subregion of the hippocampus and offer new mechanistic insight into the relationship between decreased glucose and increased seizure threshold. By establishing neuronal ATP release via pannexin hemichannels, and hippocampal adenosine A(1) receptors coupled to ATP-sensitive K(+) channels, we reveal detailed information regarding the relationship between metabolism and neuronal activity and new strategies for adenosine-based therapies in the CNS.
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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.