ArticleThe Journal of general physiology2016
Gating the glutamate gate of CLC-2 chloride channel by pore occupancy.
Article in The Journal of general physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Insights into CLC-0's Slow-Gating from Intracellular Proton Inhibition.International journal of molecular sciences · 2024Article
- Article
- CryoEM structures of the human CLC-2 voltage gated chloride channel reveal a ball and chain gating mechanism.bioRxiv : the preprint server for biology · 2023Article
- Cryo-EM structures of ClC-2 chloride channel reveal the blocking mechanism of its specific inhibitor AK-42.Nature communications · 2023Article
- Gating and anion selectivity are reciprocally regulated in TMEM16A (ANO1).The Journal of general physiology · 2022Article
- Electro-steric opening of the CLC-2 chloride channel gate.Scientific reports · 2021Article
- Kir4.1/Kir5.1 channels possess strong intrinsic inward rectification determined by a voltage-dependent K+-flux gating mechanism.The Journal of general physiology · 2021Article
- Glial Chloride Channels in the Function of the Nervous System Across Species.Advances in experimental medicine and biology · 2021Article
- Development and validation of a potent and specific inhibitor for the CLC-2 chloride channel.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Article
- Dynamical model of the CLC-2 ion channel reveals conformational changes associated with selectivity-filter gating.PLoS computational biology · 2020Article
- Molecular identification of HSPA8 as an accessory protein of a hyperpolarization-activated chloride channel from rat pulmonary vein cardiomyocytes.The Journal of biological chemistry · 2019Article
- Mouse retinal pigment epithelial cells exhibit a thiocyanate-selective conductance.American journal of physiology. Cell physiology · 2018Article
- Determining the molecular basis of voltage sensitivity in membrane proteins.The Journal of general physiology · 2018Article
- LRRC8 N termini influence pore properties and gating of volume-regulated anion channels (VRACs).The Journal of biological chemistry · 2018Article
- Extracellular protons enable activation of the calcium-dependent chloride channel TMEM16A.The Journal of physiology · 2017Article
- Revealing the activation pathway for TMEM16A chloride channels from macroscopic currents and kinetic models.Pflugers Archiv : European journal of physiology · 2016Article
- Article
- Article
- Cellular basis of ClC-2 ClThe Journal of biological chemistryArticle
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CLC-2 channels are dimeric double-barreled chloride channels that open in response to hyperpolarization. Hyperpolarization activates protopore gates that independently regulate the permeability of the pore in each subunit and the common gate that affects the permeability through both pores. CLC-2 channels lack classic transmembrane voltage-sensing domains; instead, their protopore gates (residing within the pore and each formed by the side chain of a glutamate residue) open under repulsion by permeant intracellular anions or protonation by extracellular H(+). Here, we show that voltage-dependent gating of CLC-2: (a) is facilitated when permeant anions (Cl(-), Br(-), SCN(-), and I(-)) are present in the cytosolic side; (b) happens with poorly permeant anions fluoride, glutamate, gluconate, and methanesulfonate present in the cytosolic side; (c) depends on pore occupancy by permeant and poorly permeant anions; (d) is strongly facilitated by multi-ion occupancy; (e) is absent under likely protonation conditions (pHe = 5.5 or 6.5) in cells dialyzed with acetate (an impermeant anion); and (f) was the same at intracellular pH 7.3 and 4.2; and (g) is observed in both whole-cell and inside-out patches exposed to increasing [Cl(-)]i under unlikely protonation conditions (pHe = 10). Thus, based on our results we propose that hyperpolarization activates CLC-2 mainly by driving intracellular anions into the channel pores, and that protonation by extracellular H(+) plays a minor role in dislodging the glutamate gate.
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