ArticleThe Journal of biological chemistry2011
Cross-talk between P2X4 and gamma-aminobutyric acid, type A receptors determines synaptic efficacy at a central synapse.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 61 citations in OpenAlex.
- Cell Type-Specific Expression of Purinergic P2X Receptors in the Hypothalamus.International journal of molecular sciences · 2025Review
- Regulation of GABAergic neurotransmission by purinergic receptors in brain physiology and disease.Purinergic signalling · 2025Review
- Role and therapeutic targets of P2X7 receptors in neurodegenerative diseases.Frontiers in immunology · 2024Review
- Triggering of Major Brain Disorders by Protons and ATP: The Role of ASICs and P2X Receptors.Neuroscience bulletin · 2023Review
- Article
- Increased surface P2X4 receptors by mutant SOD1 proteins contribute to ALS pathogenesis in SOD1-G93A mice.Cellular and molecular life sciences : CMLS · 2022Article
- Increased surface P2X4 receptor regulates anxiety and memory in P2X4 internalization-defective knock-in mice.Molecular psychiatry · 2021Article
- Regulation of membrane NMDA receptors by dynamics and protein interactions.The Journal of cell biology · 2021Review
- Astrocyte Clocks and Glucose Homeostasis.Frontiers in endocrinology · 2021Review
- Immunometabolic Changes in Glia - A Potential Role in the Pathophysiology of Obesity and Diabetes.Neuroscience · 2020Review
- Implication of Neuronal Versus Microglial P2X4 Receptors in Central Nervous System Disorders.Neuroscience bulletin · 2020Review
- Cross-Talk between P2X and NMDA Receptors.International journal of molecular sciences · 2020Article
- Contribution of P2X4 Receptors to CNS Function and Pathophysiology.International journal of molecular sciences · 2020Review
- Function of P2X4 Receptors Is Directly Modulated by a 1:1 Stoichiometric Interaction With 5-HTFrontiers in cellular neuroscience · 2020Article
- Alterations in GABAFrontiers in cellular neuroscience · 2019Article
- Preclinical evaluation of avermectins as novel therapeutic agents for alcohol use disorders.Psychopharmacology · 2018Review
- Reduced expression of purinergic P2X4 receptors increases voluntary ethanol intake in C57BL/6J mice.Alcohol (Fayetteville, N.Y.) · 2018Article
- Modulation of Central Synapses by Astrocyte-Released ATP and Postsynaptic P2X Receptors.Neural plasticity · 2017Review
- P2X4 Receptor Function in the Nervous System and Current Breakthroughs in Pharmacology.Frontiers in pharmacology · 2017Review
- Role of purinergic P2X4 receptors in regulating striatal dopamine homeostasis and dependent behaviors.Journal of neurochemistry · 2016Article
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The essence of neuronal function is to generate outputs in response to synaptic potentials. Synaptic integration at postsynaptic sites determines neuronal outputs in the CNS. Using immunohistochemical and electrophysiological approaches, we first reveal that steroidogenic factor 1 (SF-1) green fluorescent protein (GFP)-positive neurons in the ventromedial nucleus of the hypothalamus express P2X4 subunits that are activated by exogenous ATP. Increased membrane expression of P2X4 channels by using a peptide competing with P2X4 intracellular endocytosis motif enhances neuronal excitability of SF-1 GFP-positive neurons. This increased excitability is inhibited by a P2X receptor antagonist. Furthermore, increased surface P2X4 receptor expression significantly decreases the frequency and the amplitude of GABAergic postsynaptic currents of SF-1 GFP-positive neurons. Co-immunopurification and pulldown assays reveal that P2X4 receptors complex with aminobutyric acid, type A (GABA(A)) receptors and demonstrate that two amino acids in the carboxyl tail of the P2X4 subunit are crucial for its physical association with GABA(A) receptors. Mutation of these two residues prevents the physical association, thereby blocking cross-inhibition between P2X4 and GABA(A) receptors. Moreover, disruption of the physical coupling using competitive peptides containing the identified motif abolishes current inhibition between P2X4 and GABA(A) receptors in recombinant system and P2X4 receptor-mediated GABAergic depression in SF-1 GFP-positive neurons. Our present work thus provides evidence for cross-talk between excitatory and inhibitory receptors that appears to be crucial in determining GABAergic synaptic strength at a central synapse.
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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.