ReviewThe Journal of physiology2016
Regulation of neuronal chloride homeostasis by neuromodulators.
Review in The Journal of physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 57 citations in OpenAlex.
- Early life Oxytocin treatment Attenuates Seizure Susceptibility in Male, but not Female,bioRxiv : the preprint server for biology · 2026Article
- Orexin-A Inhibits Lipopolysaccharide-Induced Cell Migration in Cultured Mouse Astrocytes via Activation of Orexin 1 Receptor: Involvement of GABA Signaling.Journal of cellular biochemistry · 2026Article
- Neurobehavioral Signatures of Epileptogenesis: Molecular Programs, Trait-like Phenotypes, and Translational Biomarkers Beyond Seizures.International journal of molecular sciences · 2026Review
- Acceleration of axonal regeneration by GABA/Gly excitation.Anatomical science international · 2026Review
- Transcutaneous Spinal Stimulation Modulates Spinal Reflex Circuit Excitability in Persons with Spinal Cord Injury.Biomedicines · 2025Article
- KCC2 inhibition and neuronal hyperexcitability promote extrinsic apoptosis dependent upon C1q.Frontiers in molecular neuroscience · 2025Article
- Constitutive KCC2 Cell- and Synapse-Specifically Regulates NMDA Receptor Activity in the Spinal Cord.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- KCC2 reverse mode helps to clear postsynaptically released potassium at glutamatergic synapses.Cell reports · 2023Article
- Excitatory and inhibitory neuronal signaling in inflammatory and diabetic neuropathic pain.Molecular medicine (Cambridge, Mass.) · 2023Review
- KFrontiers in cellular neuroscience · 2023Article
- The serotonin 2A receptor agonist TCB-2 attenuates heavy alcohol drinking and alcohol-induced midbrain inhibitory plasticity.Addiction biology · 2022Article
- Specific Expression of KCC2 in the α Cells of Normal and Type 1 Diabetes Model Mouse Pancreatic Islets.Acta histochemica et cytochemica · 2022Article
- SNAP23 regulates KCC2 membrane insertion and activity following mZnR/GPR39 activation in hippocampalneurons.iScience · 2022Article
- Developmental Formation of the GABAergic and Glycinergic Networks in the Mouse Spinal Cord.International journal of molecular sciences · 2022Review
- NKCC1 and KCC2: Structural insights into phospho-regulation.Frontiers in molecular neuroscience · 2022Review
- Chloride Homeostasis in Developing Motoneurons.Advances in neurobiology · 2022Article
- Simultaneous Monitoring of pH and Chloride (ClInternational journal of molecular sciences · 2021Article
- AT1a-dependent GABAAmerican journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- The Role of Phospholipase C in GABAergic Inhibition and Its Relevance to Epilepsy.International journal of molecular sciences · 2021Review
- ClC-2-like Chloride Current Alterations in a Cell Model of Spinal and Bulbar Muscular Atrophy, a Polyglutamine Disease.Journal of molecular neuroscience : MN · 2021Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
KCC2 is the central regulator of neuronal Cl(-) homeostasis, and is critical for enabling strong hyperpolarizing synaptic inhibition in the mature brain. KCC2 hypofunction results in decreased inhibition and increased network hyperexcitability that underlies numerous disease states including epilepsy, neuropathic pain and neuropsychiatric disorders. The current holy grail of KCC2 biology is to identify how we can rescue KCC2 hypofunction in order to restore physiological levels of synaptic inhibition and neuronal network activity. It is becoming increasingly clear that diverse cellular signals regulate KCC2 surface expression and function including neurotransmitters and neuromodulators. In the present review we explore the existing evidence that G-protein-coupled receptor (GPCR) signalling can regulate KCC2 activity in numerous regions of the nervous system including the hypothalamus, hippocampus and spinal cord. We present key evidence from the literature suggesting that GPCR signalling is a conserved mechanism for regulating chloride homeostasis. This evidence includes: (1) the activation of group 1 metabotropic glutamate receptors and metabotropic Zn(2+) receptors strengthens GABAergic inhibition in CA3 pyramidal neurons through a regulation of KCC2; (2) activation of the 5-hydroxytryptamine type 2A serotonin receptors upregulates KCC2 cell surface expression and function, restores endogenous inhibition in motoneurons, and reduces spasticity in rats; and (3) activation of A3A-type adenosine receptors rescues KCC2 dysfunction and reverses allodynia in a model of neuropathic pain. We propose that GPCR-signals are novel endogenous Cl(-) extrusion enhancers that may regulate KCC2 function.
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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.