ArticleThe Journal of general physiology2010
Proton block of the CLC-5 Cl-/H+ exchanger.
Article in The Journal of general physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Distinct ClC-6 and ClC-7 ClThe Journal of physiology · 2023Article
- Molecular basis of ClC-6 function and its impairment in human disease.Science advances · 2023Article
- Divergent CleLife · 2020Article
- Dynamical model of the CLC-2 ion channel reveals conformational changes associated with selectivity-filter gating.PLoS computational biology · 2020Article
- Extracellular pH and intracellular phosphatidylinositol 4,5-bisphosphate control ClAmerican journal of physiology. Cell physiology · 2019Article
- Properties of single-channel and whole cell ClAmerican journal of physiology. Cell physiology · 2019Article
- Modulation of ClC-3 gating and proton/anion exchange by internal and external protons and the anion selectivity filter.The Journal of physiology · 2018Article
- Improving outcomes for patients with distal renal tubular acidosis: recent advances and challenges ahead.Pediatric health, medicine and therapeutics · 2018Review
- Renal Fanconi syndrome in distal renal tubular acidosis.Pediatric nephrology (Berlin, Germany) · 2017Article
- Overexpression of the Endosomal Anion/Proton Exchanger ClC-5 Increases Cell Susceptibility towardFrontiers in cellular and infection microbiology · 2017Article
- A pure chloride channel mutant of CLC-5 causes Dent's disease via insufficient V-ATPase activation.Pflugers Archiv : European journal of physiology · 2016Article
- Structure and gating of CLC channels and exchangers.The Journal of physiology · 2015Review
- A single point mutation reveals gating of the human ClC-5 Cl-/H+ antiporter.The Journal of physiology · 2013Article
- ClC-3 is an intracellular chloride/proton exchanger with large voltage-dependent nonlinear capacitance.ACS chemical neuroscience · 2013Article
- On the mechanism of gating charge movement of ClC-5, a human Cl(-)/H(+) antiporter.Biophysical journal · 2012Article
- Molecular dynamics investigation of Cl- and water transport through a eukaryotic CLC transporter.Biophysical journal · 2012Article
- Glutamate 268 regulates transport probability of the anion/proton exchanger ClC-5.The Journal of biological chemistry · 2012Article
- ClC-7 is a slowly voltage-gated 2Cl(-)/1H(+)-exchanger and requires Ostm1 for transport activity.The EMBO journal · 2011Article
- Anion- and proton-dependent gating of ClC-4 anion/proton transporter under uncoupling conditions.Biophysical journal · 2011Article
- Molecular Pharmacology of Kidney and Inner Ear CLC-K Chloride Channels.Frontiers in pharmacology · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
CLC-5 is a H(+)/Cl(-) exchanger that is expressed primarily in endosomes but can traffic to the plasma membrane in overexpression systems. Mutations altering the expression or function of CLC-5 lead to Dent's disease. Currents mediated by this transporter show extreme outward rectification and are inhibited by acidic extracellular pH. The mechanistic origins of both phenomena are currently not well understood. It has been proposed that rectification arises from the voltage dependence of a H(+) transport step, and that inhibition of CLC-5 currents by low extracellular pH is a result of a reduction in the driving force for exchange caused by a pH gradient. We show here that the pH dependence of CLC-5 currents arises from H(+) binding to a single site located halfway through the transmembrane electric field and driving the transport cycle in a less permissive direction, rather than a reduction in the driving force. We propose that protons bind to the extracellular gating glutamate E211 in CLC-5. It has been shown that CLC-5 becomes severely uncoupled when SCN(-) is the main charge carrier: H(+) transport is drastically reduced while the rate of anion movement is increased. We found that in these conditions, rectification and pH dependence are unaltered. This implies that H(+) translocation is not the main cause of rectification. We propose a simple transport cycle model that qualitatively accounts for these findings.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.