ArticleThe Journal of biological chemistry2011
Insights into the mechanism of pore opening of acid-sensing ion channel 1a.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Review
- Epithelial NaComprehensive Physiology · 2024Review
- Probing conformational changes during activation of ASIC1a by an optical tweezer and by methanethiosulfonate-based cross-linkers.PloS one · 2022Article
- Evolutionarily Conserved Interactions within the Pore Domain of Acid-Sensing Ion Channels.Biophysical journal · 2020Article
- ASIC3 fine-tunes bladder sensory signaling.American journal of physiology. Renal physiology · 2018Article
- Article
- Bile acids potentiate proton-activated currents inPhysiological reports · 2017Article
- Proton and non-proton activation of ASIC channels.PloS one · 2017Article
- The Thumb Domain Mediates Acid-sensing Ion Channel Desensitization.The Journal of biological chemistry · 2016Article
- Review
- ASICs and neuropeptides.Neuropharmacology · 2015Review
- The Human Acid-Sensing Ion Channel ASIC1a: Evidence for a Homotetrameric Assembly State at the Cell Surface.PloS one · 2015Article
- Prostasin interacts with the epithelial Na+ channel and facilitates cleavage of the γ-subunit by a second protease.American journal of physiology. Renal physiology · 2014Article
- Intersubunit conformational changes mediate epithelial sodium channel gating.The Journal of general physiology · 2014Article
- Electrostatic charge at position 552 affects the activation and permeation of FMRFamide-gated Na+ channels.The journal of physiological sciences : JPS · 2014Article
- Independent contribution of extracellular proton binding sites to ASIC1a activation.The Journal of biological chemistry · 2013Article
- Coupling of proton binding in extracellular domain to channel gating in acid-sensing ion channel.Journal of molecular neuroscience : MN · 2013Article
- ENaC regulation by proteases and shear stress.Current molecular pharmacology · 2013Review
- Gating transitions in the palm domain of ASIC1a.The Journal of biological chemistry · 2013Article
- Ion channels as drug targets in central nervous system disorders.Current medicinal chemistry · 2013Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Acid-sensing ion channels (ASICs) are trimeric cation channels that undergo activation and desensitization in response to extracellular acidification. The underlying mechanism coupling proton binding in the extracellular region to pore gating is unknown. Here we probed the reactivity toward methanethiosulfonate (MTS) reagents of channels with cysteine-substituted residues in the outer vestibule of the pore of ASIC1a. We found that positively-charged MTS reagents trigger pore opening of G428C. Scanning mutagenesis of residues in the region preceding the second transmembrane spanning domain indicated that the MTSET-modified side chain of Cys at position 428 interacts with Tyr-424. This interaction was confirmed by double-mutant cycle analysis. Strikingly, Y424C-G428C monomers were associated by intersubunit disulfide bonds and were insensitive to MTSET. Despite the spatial constraints introduced by these intersubunit disulfide bonds in the outer vestibule of the pore, Y424C-G428C transitions between the resting, open, and desensitized states in response to extracellular acidification. This finding suggests that the opening of the ion conductive pathway involves coordinated rotation of the second transmembrane-spanning domains.
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Registered trials
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