ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Chloride ions in the pore of glycine and GABA channels shape the time course and voltage dependence of agonist currents.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- Characterization of an open-channel structure and lateral conduction pathway in the cation-selective pentameric ligand-gated ion channel, ELIC.The Journal of general physiology · 2026Article
- Characterization of an Open-Channel Structure and Lateral Conduction Pathway in the Cation-Selective Pentameric Ligand-Gated Ion Channel, ELIC.bioRxiv : the preprint server for biology · 2025Article
- Lateral fenestrations in the extracellular domain of the glycine receptor contribute to the main chloride permeation pathway.Science advances · 2022Article
- Chloride Homeostasis in Developing Motoneurons.Advances in neurobiology · 2022Article
- The startle disease mutation α1S270T predicts shortening of glycinergic synaptic currents.The Journal of physiology · 2020Article
- Arfgef1 haploinsufficiency in mice alters neuronal endosome composition and decreases membrane surface postsynaptic GABANeurobiology of disease · 2020Article
- Relaxation of synaptic inhibitory events as a compensatory mechanism in fetal SOD spinal motor networks.eLife · 2019Article
- Triple arginines as molecular determinants for pentameric assembly of the intracellular domain of 5-HTThe Journal of general physiology · 2019Article
- GABA beyond the synapse: defining the subtype-specific pharmacodynamics of non-synaptic GABAThe Journal of physiology · 2018Article
- Bridging pro-inflammatory signals, synaptic transmission and protection in spinal explants in vitro.Molecular brain · 2018Article
- A modulatory role of ASICs on GABAergic synapses in rat hippocampal cell cultures.Molecular brain · 2016Article
- Electrophysiological Signature of Homomeric and Heteromeric Glycine Receptor Channels.The Journal of biological chemistry · 2016Article
- Maternal restraint stress delays maturation of cation-chloride cotransporters and GABAA receptor subunits in the hippocampus of rat pups at puberty.Neurobiology of stress · 2016Article
- Direct interaction of the resistance to inhibitors of cholinesterase type 3 protein with the serotonin receptor type 3A intracellular domain.Journal of neurochemistry · 2016Article
- Ethanol effects on glycinergic transmission: From molecular pharmacology to behavior responses.Pharmacological research · 2015Review
- Functional Chimeras of GLIC Obtained by Adding the Intracellular Domain of Anion- and Cation-Conducting Cys-Loop Receptors.Biochemistry · 2015Article
- Asymmetric temporal interactions of sound-evoked excitatory and inhibitory inputs in the mouse auditory midbrain.The Journal of physiology · 2014Article
- The role of intracellular linkers in gating and desensitization of human pentameric ligand-gated ion channels.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Reconstituted human TPC1 is a proton-permeable ion channel and is activated by NAADP or Ca2+.Science signaling · 2014Article
- α1F64 Residue at GABA(A) receptor binding site is involved in gating by influencing the receptor flipping transitions.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
In the vertebrate CNS, fast synaptic inhibition is mediated by GABA and glycine receptors. We recently reported that the time course of these synaptic currents is slower when intracellular chloride is high. Here we extend these findings to measure the effects of both extracellular and intracellular chloride on the deactivation of glycine and GABA currents at both negative and positive holding potentials. Currents were elicited by fast agonist application to outside-out patches from HEK-293 cells expressing rat glycine or GABA receptors. The slowing effect of high extracellular chloride on current decay was detectable only in low intracellular chloride (4 mm). Our main finding is that glycine and GABA receptors "sense" chloride concentrations because of interactions between the M2 pore-lining domain and the permeating ions. This hypothesis is supported by the observation that the sensitivity of channel gating to intracellular chloride is abolished if the channel is engineered to become cation selective or if positive charges in the external pore vestibule are eliminated by mutagenesis. The appropriate interaction between permeating ions and channel pore is also necessary to maintain the channel voltage sensitivity of gating, which prolongs current decay at depolarized potentials. Voltage dependence is abolished by the same mutations that suppress the effect of intracellular chloride and also by replacing chloride with another permeant ion, thiocyanate. These observations suggest that permeant chloride affects gating by a foot-in-the-door effect, binding to a channel site with asymmetrical access from the intracellular and extracellular sides of the membrane.
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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.