ArticleThe EMBO journal2011
Two types of chloride transporters are required for GABA(A) receptor-mediated inhibition in C. elegans.
Article in The EMBO journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- ImmatureProceedings of the National Academy of Sciences of the United States of America · 2026Article
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- Functional analysis of epilepsy-associated GABAEpilepsia open · 2024Article
- The role of NaPflugers Archiv : European journal of physiology · 2024Review
- Semantic representation of neural circuit knowledge in Caenorhabditis elegans.Brain informatics · 2023Article
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- A Meta-Analysis of Bioelectric Data in Cancer, Embryogenesis, and Regeneration.Bioelectricity · 2021Article
- EOR-1 mediates non-cell autonomous regulation of abts-1 gene expression in HSNs.microPublication biology · 2018Article
- Homeostatic Feedback Modulates the Development of Two-State Patterned Activity in a Model Serotonin Motor Circuit inThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Regulation of chromatin states and gene expression during HSN neuronal maturation is mediated by EOR-1/PLZF, MAU-2/cohesin loader, and SWI/SNF complex.Scientific reports · 2018Article
- AG3 (Bethesda, Md.) · 2018Article
- Activity of theeLife · 2016Article
- A Novel Mechanism of pH Buffering in C. elegans Glia: Bicarbonate Transport via the Voltage-Gated ClC Cl- Channel CLH-1.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- K-Cl cotransporter KCC2--a moonlighting protein in excitatory and inhibitory synapse development and function.Pflugers Archiv : European journal of physiology · 2015Review
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- Regulatory domain or CpG site variation in SLC12A5, encoding the chloride transporter KCC2, in human autism and schizophrenia.Frontiers in cellular neuroscience · 2015Article
- Genetically encoded impairment of neuronal KCC2 cotransporter function in human idiopathic generalized epilepsy.EMBO reports · 2014Article
- The voltage-gated anion channels encoded by clh-3 regulate egg laying in C. elegans by modulating motor neuron excitability.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Chloride influx through GABA-gated Cl(-) channels, the principal mechanism for inhibiting neural activity in the brain, requires a Cl(-) gradient established in part by K(+)-Cl(-) cotransporters (KCCs). We screened for Caenorhabditis elegans mutants defective for inhibitory neurotransmission and identified mutations in ABTS-1, a Na(+)-driven Cl(-)-HCO(3)(-) exchanger that extrudes chloride from cells, like KCC-2, but also alkalinizes them. While animals lacking ABTS-1 or the K(+)-Cl(-) cotransporter KCC-2 display only mild behavioural defects, animals lacking both Cl(-) extruders are paralyzed. This is apparently due to severe disruption of the cellular Cl(-) gradient such that Cl(-) flow through GABA-gated channels is reversed and excites rather than inhibits cells. Neuronal expression of both transporters is upregulated during synapse development, and ABTS-1 expression further increases in KCC-2 mutants, suggesting regulation of these transporters is coordinated to control the cellular Cl(-) gradient. Our results show that Na(+)-driven Cl(-)-HCO(3)(-) exchangers function with KCCs in generating the cellular chloride gradient and suggest a mechanism for the close tie between pH and excitability in the brain.
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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.