ArticleThe Journal of physiology2008
Gating of human ClC-2 chloride channels and regulation by carboxy-terminal domains.
Article in The Journal of physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 55 citations in OpenAlex.
- Article
- Adrenal Anion Channels: New Roles in Zona Glomerulosa Physiology and in the Pathophysiology of Primary Aldosteronism.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
- Cryo-EM structures of ClC-2 chloride channel reveal the blocking mechanism of its specific inhibitor AK-42.Nature communications · 2023Article
- Vesicular glutamate transporters are HNature communications · 2023Article
- Biallelic CLCN2 mutations cause retinal degeneration by impairing retinal pigment epithelium phagocytosis and chloride channel function.Human genetics · 2023Article
- Article
- Functional Characterization ofFrontiers in molecular neuroscience · 2022Article
- An amino-terminal point mutation increases EAAT2 anion currents without affecting glutamate transport rates.The Journal of biological chemistry · 2020Article
- Negative chronotropic and inotropic effects of lubiprostone on iPS cell-derived cardiomyocytes via activation of CFTR.BMC complementary medicine and therapies · 2020Article
- Dynamical model of the CLC-2 ion channel reveals conformational changes associated with selectivity-filter gating.PLoS computational biology · 2020Article
- Chloride Channels in Astrocytes: Structure, Roles in Brain Homeostasis and Implications in Disease.International journal of molecular sciences · 2019Review
- CLCN2 chloride channel mutations in familial hyperaldosteronism type II.Nature genetics · 2018Article
- Research and progress on ClC‑2 (Review).Molecular medicine reports · 2017Review
- Regulatory Conformational Coupling between CLC Anion Channel Membrane and Cytoplasmic Domains.Biophysical journal · 2016Article
- Role of CBS and Bateman Domains in Phosphorylation-Dependent Regulation of a CLC Anion Channel.Biophysical journal · 2016Article
- Carboxyl-terminal Truncations of ClC-Kb Abolish Channel Activation by Barttin Via Modified Common Gating and Trafficking.The Journal of biological chemistry · 2015Article
- Gating modes of calcium-activated chloride channels TMEM16A and TMEM16B.The Journal of physiology · 2015Article
- Structure and gating of CLC channels and exchangers.The Journal of physiology · 2015Review
- Basolateral sorting of chloride channel 2 is mediated by interactions between a dileucine motif and the clathrin adaptor AP-1.Molecular biology of the cell · 2015Article
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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
Eukaryotic ClC channels are dimeric proteins with each subunit forming an individual protopore. Single protopores are gated by a fast gate, whereas the slow gate is assumed to control both protopores through a cooperative movement of the two carboxy-terminal domains. We here study the role of the carboxy-terminal domain in modulating fast and slow gating of human ClC-2 channels, a ubiquitously expressed ClC-type chloride channel involved in transepithelial solute transport and in neuronal chloride homeostasis. Partial truncation of the carboxy-terminus abolishes function of ClC-2 by locking the channel in a closed position. However, unlike other isoforms, its complete removal preserves function of ClC-2. ClC-2 channels without the carboxy-terminus exhibit fast and slow gates that activate and deactivate significantly faster than in WT channels. In contrast to the prevalent view, a single carboxy-terminus suffices for normal slow gating, whereas both domains regulate fast gating of individual protopores. Our findings demonstrate that the carboxy-terminus is not strictly required for slow gating and that the cooperative gating resides in other regions of the channel protein. ClC-2 is expressed in neurons and believed to open at negative potentials and increased internal chloride concentrations after intense synaptic activity. We propose that the function of the ClC-2 carboxy-terminus is to slow down the time course of channel activation in order to stabilize neuronal excitability.
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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.