ArticleThe Journal of general physiology2012
Gating properties of the P2X2a and P2X2b receptor channels: experiments and mathematical modeling.
Article in The Journal of general physiology, 2012. 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, 36 citations in OpenAlex.
- Mechanisms underlying spontaneous and evoked calcium responses in oligodendrocyte precursor cells: A modeling investigation.PLoS computational biology · 2026Article
- Cdk5 modulates orofacial pain through P2X2/3 purinergic receptor-mediated signaling in trigeminal neurons.Frontiers in pharmacology · 2026Article
- Generalised Hodgkin-Huxley model captures human P2X and AMPA receptor currents.The Journal of physiology · 2026Article
- Using Bayesian priors to overcome non-identifiablility issues in Hidden Markov models.bioRxiv : the preprint server for biology · 2025Article
- Dilation of ion selectivity filters in cation channels.Trends in biochemical sciences · 2024Review
- Fast functional mapping of ligand-gated ion channels.Communications biology · 2023Article
- Modulation of P2X4 pore closure by magnesium, potassium, and ATP.Biophysical journal · 2022Article
- Purinoreceptors and ectonucleotidases control ATP-induced calcium waveforms and calcium-dependent responses in microglia: Roles of P2 receptors and CD39 in ATP-stimulated microglia.Frontiers in physiology · 2022Article
- Mathematical modelling of human P2X-mediated plasma membrane electrophysiology and calcium dynamics in microglia.PLoS computational biology · 2021Article
- High-affinity P2Y2 and low-affinity P2X7 receptor interaction modulates ATP-mediated calcium signaling in murine osteoblasts.PLoS computational biology · 2021Article
- Simulation of P2X-mediated calcium signalling in microglia.The Journal of physiology · 2019Article
- Opposing Roles of Calcium and Intracellular ATP on Gating of the Purinergic P2X2 Receptor Channel.International journal of molecular sciences · 2018Article
- Ethanol differentially modulates P2X4 and P2X7 receptor activity and function in BV2 microglial cells.Neuropharmacology · 2018Article
- Article
- Deciphering the regulation of P2X4 receptor channel gating by ivermectin using Markov models.PLoS computational biology · 2017Article
- On the permeation of large organic cations through the pore of ATP-gated P2X receptors.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- HSP90 Regulation of P2X7 Receptor Function Requires an Intact Cytoplasmic C-Terminus.Molecular pharmacology · 2016Article
- Insights into the channel gating of P2X receptors from structures, dynamics and small molecules.Acta pharmacologica Sinica · 2016Review
- Physical basis of apparent pore dilation of ATP-activated P2X receptor channels.Nature neuroscience · 2015Article
- Role of domain calcium in purinergic P2X2 receptor channel desensitization.American journal of physiology. Cell physiology · 2015Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Adenosine triphosphate (ATP)-gated P2X2 receptors exhibit two opposite activation-dependent changes, pore dilation and pore closing (desensitization), through a process that is incompletely understood. To address this issue and to clarify the roles of calcium and the C-terminal domain in gating, we combined biophysical and mathematical approaches using two splice forms of receptors: the full-size form (P2X2aR) and the shorter form missing 69 residues in the C-terminal domain (P2X2bR). Both receptors developed conductivity for N-methyl-D-glucamine within 2-6 s of ATP application. However, pore dilation was accompanied with a decrease rather than an increase in the total conductance, which temporally coincided with rapid and partial desensitization. During sustained agonist application, receptors continued to desensitize in calcium-independent and calcium-dependent modes. Calcium-independent desensitization was more pronounced in P2X2bR, and calcium-dependent desensitization was more pronounced in P2X2aR. In whole cell recording, we also observed use-dependent facilitation of desensitization of both receptors. Such behavior was accounted for by a 16-state Markov kinetic model describing ATP binding/unbinding and activation/desensitization. The model assumes that naive receptors open when two to three ATP molecules bind and undergo calcium-independent desensitization, causing a decrease in the total conductance, or pore dilation, causing a shift in the reversal potential. In calcium-containing media, receptor desensitization is facilitated and the use-dependent desensitization can be modeled by a calcium-dependent toggle switch. The experiments and the model together provide a rationale for the lack of sustained current growth in dilating P2X2Rs and show that receptors in the dilated state can also desensitize in the presence of calcium.
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