ArticleThe Journal of physiology2004
The voltage-dependent ClC-2 chloride channel has a dual gating mechanism.
Article in The Journal of physiology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 84 citations in OpenAlex.
- Structural basis of pH-dependent activation in a CLC transporter.Nature structural & molecular biology · 2024Article
- Article
- Biophysical and Pharmacological Insights to CLC Chloride Channels.Handbook of experimental pharmacology · 2024Article
- 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
- Vesicular CLC chloride/proton exchangers in health and diseases.Frontiers in pharmacology · 2023Review
- Case report: A frameshift mutation in CLCN2-related leukoencephalopathy and retinopathy.Frontiers in genetics · 2023Article
- 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
- 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
- Pathogenesis of Familial Hyperaldosteronism Type II: New Concepts Involving Anion Channels.Current hypertension reports · 2019Review
- Chloride Channels in Astrocytes: Structure, Roles in Brain Homeostasis and Implications in Disease.International journal of molecular sciences · 2019Review
- Leukoencephalopathy-causing CLCN2 mutations are associated with impaired ClThe Journal of physiology · 2017Article
- Research and progress on ClC‑2 (Review).Molecular medicine reports · 2017Review
- Structure and gating of CLC channels and exchangers.The Journal of physiology · 2015Review
- Tryptophan Scanning Mutagenesis Identifies the Molecular Determinants of Distinct Barttin Functions.The Journal of biological chemistry · 2015Article
- ClC-1 and ClC-2 form hetero-dimeric channels with novel protopore functions.Pflugers Archiv : European journal of physiology · 2014Article
- GlialCAM, a CLC-2 Cl(-) channel subunit, activates the slow gate of CLC chloride channels.Biophysical journal · 2014Article
- The principal conductance in Giardia lamblia trophozoites possesses functional properties similar to the mammalian ClC-2 current.Pflugers Archiv : European journal of physiology · 2014Article
- Conformational changes required for H(+)/Cl(-) exchange mediated by a CLC transporter.Nature structural & molecular biology · 2014Article
- CLC channel function and dysfunction in health and disease.Frontiers in physiology · 2014Review
- Chloride channelopathies of ClC-2.International journal of molecular sciences · 2013Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Functional and structural studies demonstrate that Cl(-) channels of the ClC family have a dimeric double-barrelled structure, with each monomer contributing an identical pore. Single protopore gating is a fast process dependent on Cl(-) interaction within the selectivity filter and in ClC-0 has a low temperature coefficient over a 10 degrees C range (Q(10)). A slow gating process closes both protopores simultaneously, has a high Q(10), is facilitated by extracellular Zn(2+) and Cd(2+) and is abolished or markedly reduced by mutation of a cysteine conserved in ClC-0, -1 and -2. In order to test the hypothesis that similar slow and fast gates exist in the widely expressed ClC-2 Cl(-) channel we have investigated the effects of these manoeuvres on ClC-2. We find that the time constants of both components of the double-exponential hyperpolarization-dependent activation (and deactivation) processes have a high temperature dependence, with Q(10) values of about 4-5, suggesting important conformational changes of the channel. Mutating C256 (equivalent to C212 in ClC-0) to A, led to a significant fraction of constitutively open channels at all potentials. Activation time constants were not affected but deactivation was slower and significantly less temperature dependent in the C256A mutant. Extracellular Cd(2+), that inhibits wild-type (WT) channels almost fully, inhibited C256A only by 50%. In the WT, the time constants for opening were not affected by Cd(2+) but deactivation at positive potentials was accelerated by Cd(2+). This effect was absent in the C256A mutant. The effect of intracellular Cl(-) on channel activation was unchanged in the C256A mutant. Collectively our results strongly support the hypothesis that ClC-2 possesses a common gate and that part of the current increase induced by hyperpolarization represents an opening of the common gate. In contrast to the gating in ClC-0, the protopore gate and the common gate of ClC-2 do not appear to be independent.
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