ArticleACS chemical neuroscience2013
ClC-3 is an intracellular chloride/proton exchanger with large voltage-dependent nonlinear capacitance.
Article in ACS chemical neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed.
- Folding and Oligomerization of CLC Channels and Transporters.Chemical reviews · 2026Review
- Dominant Action ofCells · 2025Article
- Endosomal 2Cl-/H+ exchangers regulate neuronal excitability by tuning Kv7/KCNQ channel density.Brain : a journal of neurology · 2025Article
- A large-scale evolutionary and structural analysis of CLC channels and transporters.Protein science : a publication of the Protein Society · 2025Article
- Disruption of ClC-3-mediated 2ClScientific reports · 2025Article
- 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
- The PDE4 Inhibitors Roflumilast and Rolipram Rescue ADO2 Osteoclast Resorption Dysfunction.Calcified tissue international · 2024Article
- Distinct ClC-6 and ClC-7 ClThe Journal of physiology · 2023Article
- Biophysical Aspects of Neurodegenerative and Neurodevelopmental Disorders Involving Endo-/Lysosomal CLC ClLife (Basel, Switzerland) · 2023Review
- Chloride Channel-3 (ClC-3) Modifies the Trafficking of Leucine-Rich Repeat-Containing 8A (LRRC8A) Anion Channels.The Journal of membrane biology · 2023Article
- Novel variants in theFrontiers in neurology · 2023Article
- Chromogranin B (CHGB) is dimorphic and responsible for dominant anion channels delivered to cell surface via regulated secretion.Frontiers in molecular neuroscience · 2023Article
- Regulated Restructuring of Mucins During Secretory Granule Maturation In Vivo.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Chloride channels with ClC-1-like properties differentially regulate the excitability of dopamine receptor D1- and D2-expressing striatal medium spiny neurons.American journal of physiology. Cell physiology · 2022Article
- The Role of the Lysosomal ClCells · 2022Review
- ClC-3 regulates the excitability of nociceptive neurons and is involved in inflammatory processes within the spinal sensory pathway.Frontiers in cellular neuroscience · 2022Article
- Functional Characterization ofFrontiers in molecular neuroscience · 2022Article
- Roles of Endomembrane Alkali Cation/Proton Exchangers in Synaptic Function and Neurodevelopmental Disorders.Frontiers in physiology · 2022Review
- Pathophysiological role of ion channels and transporters in gastrointestinal mucosal diseases.Cellular and molecular life sciences : CMLS · 2021Review
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4 authors.
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No grant is acknowledged in the PubMed record.
Abstract
The chloride/proton exchangers ClC-3, ClC-4 and ClC-5 are localized in distinct intracellular compartments and regulate their luminal acidity. We used electrophysiology combined with fluorescence pH measurements to compare the functions of these three transporters. Since the expression of WT ClC-3 in the surface membrane was negligible, we removed an N-terminal retention signal for standard electrophysiological characterization of this isoform. This construct (ClC-313-19A) mediated outwardly rectifying coupled Cl(-)/H(+) antiport resembling the properties of ClC-4 and ClC-5. In addition, ClC-3 exhibited large electric capacitance, exceeding the nonlinear capacitances of ClC-4 and ClC-5. Mutations of the proton glutamate, a conserved residue at the internal side of the protein, decreased ion transport but increased nonlinear capacitances in all three isoforms. This suggests that nonlinear capacitances in mammalian ClC transporters are regulated in a similar manner. However, the voltage dependence and the amplitudes of these capacitances differed strongly between the investigated isoforms. Our results indicate that ClC-3 is specialized in mainly performing incomplete capacitive nontransporting cycles, that ClC-4 is an effective coupled transporter, and that ClC-5 displays an intermediate phenotype. Mathematical modeling showed that such functional differences would allow differential regulation of luminal acidification and chloride concentration in intracellular compartments.
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