ArticleBritish journal of pharmacology2009
Cysteine-independent inhibition of the CFTR chloride channel by the cysteine-reactive reagent sodium (2-sulphonatoethyl) methanethiosulphonate.
Article in British journal of pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Two positively charged amino acid side-chains in the inner vestibule of the CFTR channel pore play analogous roles in controlling anion binding and anion conductance.Cellular and molecular life sciences : CMLS · 2021Article
- Contribution of the eighth transmembrane segment to the function of the CFTR chloride channel pore.Cellular and molecular life sciences : CMLS · 2019Article
- Conformational change of the extracellular parts of the CFTR protein during channel gating.Cellular and molecular life sciences : CMLS · 2018Article
- Cytoplasmic pathway followed by chloride ions to enter the CFTR channel pore.Cellular and molecular life sciences : CMLS · 2016Article
- Glutathione release through connexin hemichannels: Implications for chemical modification of pores permeable to large molecules.The Journal of general physiology · 2015Article
- Functional Architecture of the Cytoplasmic Entrance to the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel Pore.The Journal of biological chemistry · 2015Article
- Metal bridges illuminate transmembrane domain movements during gating of the cystic fibrosis transmembrane conductance regulator chloride channel.The Journal of biological chemistry · 2014Article
- Bacterial cell wall. MurJ is the flippase of lipid-linked precursors for peptidoglycan biogenesis.Science (New York, N.Y.) · 2014Article
- Relative contribution of different transmembrane segments to the CFTR chloride channel pore.Pflugers Archiv : European journal of physiology · 2014Article
- Cystic fibrosis transmembrane conductance regulator chloride channel blockers: Pharmacological, biophysical and physiological relevance.World journal of biological chemistry · 2014Review
- Relative movements of transmembrane regions at the outer mouth of the cystic fibrosis transmembrane conductance regulator channel pore during channel gating.The Journal of biological chemistry · 2012Article
- Role of the juxtamembrane region of cytoplasmic loop 3 in the gating and conductance of the cystic fibrosis transmembrane conductance regulator chloride channel.Biochemistry · 2012Article
- Alternating access to the transmembrane domain of the ATP-binding cassette protein cystic fibrosis transmembrane conductance regulator (ABCC7).The Journal of biological chemistry · 2012Article
- Cystic fibrosis transmembrane conductance regulator: a molecular model defines the architecture of the anion conduction path and locates a "bottleneck" in the pore.Biochemistry · 2012Article
- Functional differences in pore properties between wild-type and cysteine-less forms of the CFTR chloride channel.The Journal of membrane biology · 2011Article
- Functional arrangement of the 12th transmembrane region in the CFTR chloride channel pore based on functional investigation of a cysteine-less CFTR variant.Pflugers Archiv : European journal of physiology · 2011Article
- Alignment of transmembrane regions in the cystic fibrosis transmembrane conductance regulator chloride channel pore.The Journal of general physiology · 2011Article
- Comparison of protein behavior between wild-type and G601S hERG in living cells by fluorescence correlation spectroscopy.The journal of physiological sciences : JPS · 2011Article
- Changes in accessibility of cytoplasmic substances to the pore associated with activation of the cystic fibrosis transmembrane conductance regulator chloride channel.The Journal of biological chemistry · 2010Article
- Regulation of conductance by the number of fixed positive charges in the intracellular vestibule of the CFTR chloride channel pore.The Journal of general physiology · 2010Article
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Authors and funding
4 authors.
Funding
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Abstract
background and purposeMethanethiosulphonate (MTS) reagents are used extensively to modify covalently cysteine side chains in ion channel structure-function studies. We have investigated the interaction between a widely used negatively charged MTS reagent, (2-sulphonatoethyl) methanethiosulphonate (MTSES), and the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel. EXPERIMENTAL APPROACH: Patch clamp recordings were used to study a 'cys-less' variant of human CFTR, in which all 18 endogenous cysteine residues have been removed by mutagenesis, expressed in mammalian cell lines. Use of excised inside-out membrane patches allowed MTS reagents to be applied to the cytoplasmic face of active channels. KEY
resultsIntracellular application of MTSES, but not the positively charged MTSET, inhibited the function of cys-less CFTR. Inhibition was voltage dependent, with a K(d) of 1.97 mmol x L(-1) at -80 mV increasing to 36 mmol x L(-1) at +80 mV. Inhibition was completely reversed on washout of MTSES, inconsistent with covalent modification of the channel protein. At the single channel level, MTSES caused a concentration-dependent reduction in unitary current amplitude. This inhibition was strengthened when extracellular Cl(-) concentration was decreased. CONCLUSIONS AND IMPLICATIONS: Our results indicate that MTSES inhibits the function of CFTR in a manner that is independent of its ability to modify cysteine residues covalently. Instead, we suggest that MTSES functions as an open channel blocker that enters the CFTR channel pore from its cytoplasmic end to physically occlude Cl(-) permeation. Given the very widespread use of MTS reagents in functional studies, our findings offer a broadly applicable caveat to the interpretation of results obtained from such studies.
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