ArticlePflugers Archiv : European journal of physiology2013
Regulation of ClC-2 gating by intracellular ATP.
Article in Pflugers Archiv : European journal of physiology, 2013. 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.
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- 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
- Molecular basis of ClC-6 function and its impairment in human disease.Science advances · 2023Article
- Molecular mechanism underlying regulation of Arabidopsis CLCa transporter by nucleotides and phospholipids.Nature communications · 2023Article
- Cryo-EM structures of ClC-2 chloride channel reveal the blocking mechanism of its specific inhibitor AK-42.Nature communications · 2023Article
- Identification and validation of a signature involving voltage-gated chloride ion channel genes for prediction of prostate cancer recurrence.Frontiers in endocrinology · 2022Article
- Electro-steric opening of the CLC-2 chloride channel gate.Scientific reports · 2021Article
- 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
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- An amino-terminal point mutation increases EAAT2 anion currents without affecting glutamate transport rates.The Journal of biological chemistry · 2020Article
- Cryo-EM structure of the lysosomal chloride-proton exchanger CLC-7 in complex with OSTM1.eLife · 2020Article
- Metabolic energy sensing by mammalian CLC anion/proton exchangers.EMBO reports · 2020Article
- The Ion Channel and GPCR Toolkit of Brain Capillary Pericytes.Frontiers in cellular neuroscience · 2020Review
- Pathogenesis of Familial Hyperaldosteronism Type II: New Concepts Involving Anion Channels.Current hypertension reports · 2019Review
- CLCN2 chloride channel mutations in familial hyperaldosteronism type II.Nature genetics · 2018Article
- Research and progress on ClC‑2 (Review).Molecular medicine reports · 2017Review
- Reduced Membrane Insertion of CLC-K by V33L Barttin Results in Loss of Hearing, but Leaves Kidney Function Intact.Frontiers in physiology · 2017Article
- ClC Channels and Transporters: Structure, Physiological Functions, and Implications in Human Chloride Channelopathies.Frontiers in pharmacology · 2017Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ClC-2 is a voltage-dependent chloride channel that activates slowly at voltages negative to the chloride reversal potential. Adenosine triphosphate (ATP) and other nucleotides have been shown to bind to carboxy-terminal cystathionine-ß-synthase (CBS) domains of ClC-2, but the functional consequences of binding are not sufficiently understood. We here studied the effect of nucleotides on channel gating using single-channel and whole-cell patch clamp recordings on transfected mammalian cells. ATP slowed down macroscopic activation and deactivation time courses in a dose-dependent manner. Removal of the complete carboxy-terminus abolishes the effect of ATP, suggesting that CBS domains are necessary for ATP regulation of ClC-2 gating. Single-channel recordings identified long-lasting closed states of ATP-bound channels as basis of this gating deceleration. ClC-2 channel dimers exhibit two largely independent protopores that are opened and closed individually as well as by a common gating process. A seven-state model of common gating with altered voltage dependencies of opening and closing transitions for ATP-bound states correctly describes the effects of ATP on macroscopic and microscopic ClC-2 currents. To test for a potential pathophysiological impact of ClC-2 regulation by ATP, we studied ClC-2 channels carrying naturally occurring sequence variants found in patients with idiopathic generalized epilepsy, G715E, R577Q, and R653T. All naturally occurring sequence variants accelerate common gating in the presence but not in the absence of ATP. We propose that ClC-2 uses ATP as a co-factor to slow down common gating for sufficient electrical stability of neurons under physiological conditions.
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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.