ArticleThe Journal of general physiology2011
Ion access pathway to the transmembrane pore in P2X receptor channels.
Article in The Journal of general physiology, 2011. 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, 68 citations in OpenAlex.
- Mechanisms of ligand recognition and channel opening for P2X2 receptors in lipid nanodiscs.Science advances · 2026Article
- Mechanisms of ligand recognition and channel opening for P2X2 receptors in lipid nanodiscs.bioRxiv : the preprint server for biology · 2025Article
- Dilation of ion selectivity filters in cation channels.Trends in biochemical sciences · 2024Review
- Article
- Lateral fenestrations in the extracellular domain of the glycine receptor contribute to the main chloride permeation pathway.Science advances · 2022Article
- Accessibility of ENaC extracellular domain central core residues.The Journal of biological chemistry · 2022Article
- Role of Conserved Residues and F322 in the Extracellular Vestibule of the Rat P2X7 Receptor in Its Expression, Function and Dye Uptake Ability.International journal of molecular sciences · 2020Article
- Molecular Modeling Applied to the Discovery of New Lead Compounds for P2 Receptors Based on Natural Sources.Frontiers in pharmacology · 2020Review
- P2X4 ReceptorFrontiers in pharmacology · 2017Article
- Article
- P2X receptors.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2016Review
- Inter-subunit disulfide locking of the human P2X3 receptor elucidates ectodomain movements associated with channel gating.Purinergic signalling · 2016Article
- Conductance of P2X4 purinergic receptor is determined by conformational equilibrium in the transmembrane region.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Insights into the channel gating of P2X receptors from structures, dynamics and small molecules.Acta pharmacologica Sinica · 2016Review
- Glutathione release through connexin hemichannels: Implications for chemical modification of pores permeable to large molecules.The Journal of general physiology · 2015Article
- Roles of the lateral fenestration residues of the P2X₄ receptor that contribute to the channel function and the deactivation effect of ivermectin.Purinergic signalling · 2015Article
- Role of domain calcium in purinergic P2X2 receptor channel desensitization.American journal of physiology. Cell physiology · 2015Article
- Key sites for P2X receptor function and multimerization: overview of mutagenesis studies on a structural basis.Current medicinal chemistry · 2015Review
- Ectodomain movements of an ATP-gated ion channel (P2X2 receptor) probed by disulfide locking.The Journal of biological chemistry · 2014Article
- Direct gating of ATP-activated ion channels (P2X2 receptors) by lipophilic attachment at the outer end of the second transmembrane domain.The Journal of biological chemistry · 2014Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
P2X receptors are trimeric cation channels that open in response to the binding of adenosine triphosphate (ATP) to a large extracellular domain. The x-ray structure of the P2X4 receptor from zebrafish (zfP2X4) receptor reveals that the extracellular vestibule above the gate opens to the outside through lateral fenestrations, providing a potential pathway for ions to enter and exit the pore. The extracellular region also contains a void at the central axis, providing a second potential pathway. To investigate the energetics of each potential ion permeation pathway, we calculated the electrostatic free energy by solving the Poisson-Boltzmann equation along each of these pathways in the zfP2X4 crystal structure and a homology model of rat P2X2 (rP2X2). We found that the lateral fenestrations are energetically favorable for monovalent cations even in the closed-state structure, whereas the central pathway presents strong electrostatic barriers that would require structural rearrangements to allow for ion accessibility. To probe ion accessibility along these pathways in the rP2X2 receptor, we investigated the modification of introduced Cys residues by methanethiosulfonate (MTS) reagents and constrained structural changes by introducing disulfide bridges. Our results show that MTS reagents can permeate the lateral fenestrations, and that these become larger after ATP binding. Although relatively small MTS reagents can access residues in one of the vestibules within the central pathway, no reactive positions were identified in the upper region of this pathway, and disulfide bridges that constrain movements in that region do not prevent ion conduction. Collectively, these results suggest that ions access the pore using the lateral fenestrations, and that these breathe as the channel opens. The accessibility of ions to one of the chambers in the central pathway likely serves a regulatory function.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.