ArticleFrontiers in cellular neuroscience2014
Involvement of ClC-3 chloride/proton exchangers in controlling glutamatergic synaptic strength in cultured hippocampal neurons.
Article in Frontiers in cellular neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- The nonexcitable smooth muscle: remodeling the smooth muscle ion transport toolkit in disease.Physiological reviews · 2026Review
- A large-scale evolutionary and structural analysis of CLC channels and transporters.Protein science : a publication of the Protein Society · 2025Article
- Human stem cell-based models to study synaptic dysfunction and cognition in schizophrenia: A narrative review.Schizophrenia research · 2024Review
- Experience with the Ketogenic Diet in a Boy withBalkan journal of medical genetics : BJMG · 2023Article
- Vesicular glutamate transporters are HNature communications · 2023Article
- Opponent vesicular transporters regulate the strength of glutamatergic neurotransmission in a C. elegans sensory circuit.Nature communications · 2021Article
- Multi-omics analyses of cognitive traits and psychiatric disorders highlights brain-dependent mechanisms.Human molecular genetics · 2021Article
- Neurodegeneration Upon Dysfunction of Endosomal/Lysosomal CLC Chloride Transporters.Frontiers in cell and developmental biology · 2021Review
- Uncoupling endosomal CLC chloride/proton exchange causes severe neurodegeneration.The EMBO journal · 2020Article
- A transcriptome-wide association study implicates specific pre- and post-synaptic abnormalities in schizophrenia.Human molecular genetics · 2020Article
- Expression of plasma membrane calcium ATPases confers CaScientific reports · 2019Article
- Modulation of ClC-3 gating and proton/anion exchange by internal and external protons and the anion selectivity filter.The Journal of physiology · 2018Article
- The Regulatory Mechanisms and Therapeutic Potential of MicroRNAs: From Chronic Pain to Morphine Tolerance.Frontiers in molecular neuroscience · 2018Review
- VGLUT1 functions as a glutamate/proton exchanger with chloride channel activity in hippocampal glutamatergic synapses.Nature communications · 2017Article
- Preferential association with ClC-3 permits sorting of ClC-4 into endosomal compartments.The Journal of biological chemistry · 2017Article
- Open chromatin profiling of human postmortem brain infers functional roles for non-coding schizophrenia loci.Human molecular genetics · 2017Article
- ClC Channels and Transporters: Structure, Physiological Functions, and Implications in Human Chloride Channelopathies.Frontiers in pharmacology · 2017Review
- Gene expression elucidates functional impact of polygenic risk for schizophrenia.Nature neuroscience · 2016Article
- Vesicular glutamate transporters as anion channels?Pflugers Archiv : European journal of physiology · 2016Review
- ClC-3 Expression and Its Association with Hyperglycemia Induced HT22 Hippocampal Neuronal Cell Apoptosis.Journal of diabetes research · 2016Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ClC-3 is a member of the CLC family of anion channels and transporters that localizes to early and late endosomes as well as to synaptic vesicles (SV). Its genetic disruption in mouse models results in pronounced hippocampal and retinal neurodegeneration, suggesting that ClC-3 might be important for normal excitatory and/or inhibitory neurotransmission in central neurons. To characterize the role of ClC-3 in glutamate accumulation in SV we compared glutamatergic synaptic transmission in cultured hippocampal neurons from WT and Clcn3-/- mice. In Clcn3-/- neurons the amplitude and frequency of miniature as well as the amplitudes of action-potential evoked EPSCs were significantly increased as compared to WT neurons. The low-affinity competitive AMPA receptor antagonist γ-DGG reduced the quantal size of synaptic events more effectively in WT than in Clcn3-/- neurons, whereas no difference was observed for the high-affinity competitive non-NMDA antagonist NBQX. Paired pulse ratios of evoked EPSCs were significantly reduced, whereas the size of the readily releasable pool was not affected by the genetic ablation of ClC-3. Electron microscopy revealed increased volumes of SV in hippocampi of Clcn3-/- mice. Our findings demonstrate that ClC-3 controls fast excitatory synaptic transmission by regulating the amount of neurotransmitter as well as the release probability of SV. These results provide novel insights into the role of ClC-3 in synaptic transmission and identify excessive glutamate release as a likely basis of neurodegeneration in Clcn3-/-.
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