ArticleThe Journal of biological chemistry2010
The ClC-3 Cl-/H+ antiporter becomes uncoupled at low extracellular pH.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- CLN3 mediates chloride efflux from lysosomes.Neuron · 2026Article
- Clues and new evidences in arterial hypertension: unmasking the role of the chloride anion.Pflugers Archiv : European journal of physiology · 2022Review
- Loss of Chloride Channel 6 (CLC-6) Affects Vascular Smooth Muscle Contractility and Arterial Stiffness via Alterations to Golgi Calcium Stores.Hypertension (Dallas, Tex. : 1979) · 2021Article
- Glial Chloride Channels in the Function of the Nervous System Across Species.Advances in experimental medicine and biology · 2021Article
- Cell Death Induction and Protection by Activation of Ubiquitously Expressed Anion/Cation Channels. Part 2: Functional and Molecular Properties of ASOR/PAC Channels and Their Roles in Cell Volume Dysregulation and Acidotoxic Cell Death.Frontiers in cell and developmental biology · 2021Review
- Determinants of Phagosomal pH During Host-Pathogen Interactions.Frontiers in cell and developmental biology · 2020Review
- Extracellular pH and intracellular phosphatidylinositol 4,5-bisphosphate control ClAmerican journal of physiology. Cell physiology · 2019Article
- Acid- and Volume-Sensitive Chloride Currents in Microglial Cells.International journal of molecular sciences · 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
- Characterization of constitutive and acid-induced outwardly rectifying chloride currents in immortalized mouse distal tubular cells.Biochimica et biophysica acta. General subjects · 2017Article
- The LRRC8A Mediated "Swell Activated" Chloride Conductance Is Dispensable for Vacuolar Homeostasis in Neutrophils.Frontiers in pharmacology · 2017Article
- Distinct pharmacological and molecular properties of the acid-sensitive outwardly rectifying (ASOR) anion channel from those of the volume-sensitive outwardly rectifying (VSOR) anion channel.Pflugers Archiv : European journal of physiology · 2016Article
- A spatial model of fluid recycling in the airways of the lung.Journal of theoretical biology · 2015Article
- Salt, chloride, bleach, and innate host defense.Journal of leukocyte biology · 2015Review
- Structural requirements of steroidal agonists of transient receptor potential melastatin 3 (TRPM3) cation channels.British journal of pharmacology · 2014Article
- Temperature sensitivity of acid-sensitive outwardly rectifying (ASOR) anion channels in cortical neurons is involved in hypothermic neuroprotection against acidotoxic necrosis.Channels (Austin, Tex.) · 2014Article
- Involvement of tumor acidification in brain cancer pathophysiology.Frontiers in physiology · 2013Review
- Acid-sensitive outwardly rectifying (ASOR) anion channels in human epithelial cells are highly sensitive to temperature and independent of ClC-3.Pflugers Archiv : European journal of physiology · 2013Article
- ClC-3 is an intracellular chloride/proton exchanger with large voltage-dependent nonlinear capacitance.ACS chemical neuroscience · 2013Article
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5 authors.
Funding
Abstract
Adenovirus expressing ClC-3 (Ad-ClC-3) induces Cl(-)/H(+) antiport current (I(ClC-3)) in HEK293 cells. The outward rectification and time dependence of I(ClC-3) closely resemble an endogenous HEK293 cell acid-activated Cl(-) current (ICl(acid)) seen at extracellular pH <or= 5.5. ICl(acid) was present in smooth muscle cells from wild-type but not ClC-3 null mice. We therefore sought to determine whether these currents were related. ICl(acid) was larger in cells expressing Ad-ClC-3. Protons shifted the reversal potential (E(rev)) of I(ClC-3) between pH 8.2 and 6.2, but not pH 6.2 and 5.2, suggesting that Cl(-) and H(+) transport become uncoupled at low pH. At pH 4.0 E(rev) was completely Cl(-) dependent (55.8 +/- 2.3 mV/decade). Several findings linked ClC-3 with native ICl(acid); 1) RNA interference directed at ClC-3 message reduced native ICl(acid); 2) removal of the extracellular "fast gate" (E224A) produced large currents that were pH-insensitive; and 3) wild-type I(ClC-3) and ICl(acid) were both inhibited by (2-sulfonatoethyl)methanethiosulfonate (MTSES; 10-500 microm)-induced alkanethiolation at exposed cysteine residues. However, a ClC-3 mutant lacking four extracellular cysteine residues (C103_P130del) was completely resistant to MTSES. C103_P130del currents were still acid-activated, but could be distinguished from wild-type I(ClC-3) and from native ICl(acid) by a much slower response to low pH. Thus, ClC-3 currents are activated by protons and ClC-3 protein may account for native ICl(acid). Low pH uncouples Cl(-)/H(+) transport so that at pH 4.0 ClC-3 behaves as an anion-selective channel. These findings have important implications for the biology of Cl(-)/H(+) antiporters and perhaps for pH regulation in highly acidic intracellular compartments.
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