ArticleThe Journal of physiology2002
Functional characterization of recombinant human ClC-4 chloride channels in cultured mammalian cells.
Article in The Journal of physiology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 59 citations in OpenAlex.
- Molecular basis of ClC-6 function and its impairment in human disease.Science advances · 2023Article
- 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
- Extracellular pH and intracellular phosphatidylinositol 4,5-bisphosphate control ClAmerican journal of physiology. Cell physiology · 2019Article
- Preferential association with ClC-3 permits sorting of ClC-4 into endosomal compartments.The Journal of biological chemistry · 2017Article
- Regulation of ClC-2 gating by intracellular ATP.Pflugers Archiv : European journal of physiology · 2013Article
- The ClC-3 chloride channel and osmoregulation in the European sea bass, Dicentrarchus labrax.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2013Article
- Anion- and proton-dependent gating of ClC-4 anion/proton transporter under uncoupling conditions.Biophysical journal · 2011Article
- ClC transporters: discoveries and challenges in defining the mechanisms underlying function and regulation of ClC-5.Pflugers Archiv : European journal of physiology · 2010Review
- The ClC-3 Cl-/H+ antiporter becomes uncoupled at low extracellular pH.The Journal of biological chemistry · 2010Article
- Channel-like slippage modes in the human anion/proton exchanger ClC-4.The Journal of general physiology · 2009Article
- Insights into the ClC-4 transport mechanism from studies of Zn2+ inhibition.Biophysical journal · 2008Article
- To ATP or not to ATP: this is the question.The Journal of general physiology · 2008Article
- Nucleotides bind to the C-terminus of ClC-5.The Biochemical journal · 2006Article
- The kinetics of synaptic vesicle reacidification at hippocampal nerve terminals.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2006Article
- Identification and functional characterization of a voltage-gated chloride channel and its novel splice variant in taste bud cells.The Journal of biological chemistry · 2005Article
- Characterization of a proton-activated, outwardly rectifying anion channel.The Journal of physiology · 2005Article
- Article
- Identification of an N-terminal amino acid of the CLC-3 chloride channel critical in phosphorylation-dependent activation of a CaMKII-activated chloride current.The Journal of physiology · 2004Article
- Conduction mechanisms of chloride ions in ClC-type channels.Biophysical journal · 2004Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Members of the ClC chloride channel family participate in several physiological processes and are linked to human genetic diseases. The physiological role of ClC-4 is unknown and previous detailed characterizations of recombinant human ClC-4 (hClC-4) have provided conflicting results. To re-examine the hClC-4 phenotype, recombinant hClC-4 was expressed in three distinct mammalian cell lines and characterized using patch-clamp techniques. In all cells, the expression of hClC-4 generated strongly outward-rectifying Cl(-) currents with the conductance sequence: SCN(-) >> NO(3)(-) >> Cl(-) > Br(-) approximate I(-) >> aspartate. Continuous activity of hClC-4 was sustained to different degrees by internal nucleotides: ATP approximately ATPgammaS >> AMP-PNP approximate GTP > ADP. Although non-hydrolysable nucleotides are sufficient for channel function, ATP hydrolysis is required for full activity. Changing the extracellular (2 mM or nominal Ca(2+)-free) or intracellular Ca(2+) (25 or 250 nM) concentration did not alter hClC-4 currents. Acidification of external pH (pH(o)) inhibited hClC-4 currents (half-maximal inhibition approximate 6.19), whereas neither external alkalinization to pH 8.4 nor internal acidification to pH 6.0 reduced current levels. Single-channel recordings demonstrated a Cl(-) channel active only at depolarizing potentials with a slope conductance of approximately 3 pS. Acidic pH(o) did not alter single-channel conductance. We conclude that recombinant hClC-4 encodes a small-conductance, nucleotide-dependent, Ca(2+)-independent outward-rectifying chloride channel that is inhibited by external acidification. This detailed characterization will be highly valuable in comparisons of hClC-4 function with native chloride channel activities and for future structure-function correlations.
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