ArticleThe Journal of general physiology2009
Channel-like slippage modes in the human anion/proton exchanger ClC-4.
Article in The Journal of general physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- SLC26A11 is an atypical solute carrier with dual transport-channel function mediating lysosomal sulfate transport.Nature communications · 2026Article
- Expanding the genetic and phenotypic relevance of CLCN4 variants in neurodevelopmental condition: 13 new patients.Journal of neurology · 2024Article
- Genotype-phenotype correlation in CLCN4-related developmental and epileptic encephalopathy.Human genetics · 2024Article
- Structural basis of pH-dependent activation in a CLC transporter.Nature structural & molecular biology · 2024Article
- Article
- Vesicular glutamate transporters are HNature communications · 2023Article
- The Role of the Lysosomal ClCells · 2022Review
- Functional Characterization ofFrontiers in molecular neuroscience · 2022Article
- Not so transport incompetent after all: Revisiting a CLC-7 mutant sheds new mechanistic light on lysosomal physiology.The Journal of general physiology · 2021Article
- An amino-terminal point mutation increases EAAT2 anion currents without affecting glutamate transport rates.The Journal of biological chemistry · 2020Article
- SLC26A7 constitutes the thiocyanate-selective anion conductance of the basolateral membrane of the retinal pigment epithelium.American journal of physiology. Cell physiology · 2020Article
- Modulating the Chemical Transport Properties of a Transmembrane Antiporter via Alternative Anion Flux.Journal of the American Chemical Society · 2018Article
- Mouse retinal pigment epithelial cells exhibit a thiocyanate-selective conductance.American journal of physiology. Cell physiology · 2018Article
- Modulation of ClC-3 gating and proton/anion exchange by internal and external protons and the anion selectivity filter.The Journal of physiology · 2018Article
- Preferential association with ClC-3 permits sorting of ClC-4 into endosomal compartments.The Journal of biological chemistry · 2017Article
- ClC Channels and Transporters: Structure, Physiological Functions, and Implications in Human Chloride Channelopathies.Frontiers in pharmacology · 2017Review
- Multifunctional ion transport properties of human SLC4A11: comparison of the SLC4A11-B and SLC4A11-C variants.American journal of physiology. Cell physiology · 2016Article
- Molecular Basis for Differential Anion Binding and Proton Coupling in the Cl(-)/H(+) Exchanger ClC-ec1.Journal of the American Chemical Society · 2016Article
- Molecular physiology of EAAT anion channels.Pflugers Archiv : European journal of physiology · 2016Review
- Impaired surface membrane insertion of homo- and heterodimeric human muscle chloride channels carrying amino-terminal myotonia-causing mutations.Scientific reports · 2015Article
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2 authors.
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Abstract
The ClC family encompasses two classes of proteins with distinct transport functions: anion channels and transporters. ClC-type transporters usually mediate secondary active anion-proton exchange. However, under certain conditions they assume slippage mode behavior in which proton and anion transport are uncoupled, resulting in passive anion fluxes without associated proton movements. Here, we use patch clamp and intracellular pH recordings on transfected mammalian cells to characterize exchanger and slippage modes of human ClC-4, a member of the ClC transporter branch. We found that the two transport modes differ in transport mechanisms and transport rates. Nonstationary noise analysis revealed a unitary transport rate of 5 x 10(5) s(-1) at +150 mV for the slippage mode, indicating that ClC-4 functions as channel in this mode. In the exchanger mode, unitary transport rates were 10-fold lower. Both ClC-4 transport modes exhibit voltage-dependent gating, indicating that there are active and non-active states for the exchanger as well as for the slippage mode. ClC-4 can assume both transport modes under all tested conditions, with exchanger/channel ratios determined by the external anion. We propose that binding of transported anions to non-active states causes transition from slippage into exchanger mode. Binding and unbinding of anions is very rapid, and slower transitions of liganded and non-liganded states into active conformations result in a stable distribution between the two transport modes. The proposed mechanism results in anion-dependent conversion of ClC-type exchanger into an anion channel with typical attributes of ClC anion channels.
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