ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
Facilitation of P2X7 receptor currents and membrane blebbing via constitutive and dynamic calmodulin binding.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 117 citations in OpenAlex.
- Generalised Hodgkin-Huxley model captures human P2X and AMPA receptor currents.The Journal of physiology · 2026Article
- P2X7 Receptor in Rare Diseases: Shared Molecular Mechanisms and Therapeutic Implications.Journal of inflammation research · 2026Review
- New insights into pathogenisis and therapies of P2X7R in Parkinson's disease.NPJ Parkinson's disease · 2025Review
- Modulating Neuroinflammation as a Prospective Therapeutic Target in Alzheimer's Disease.Cells · 2025Review
- P2X7 Receptor: an Emerging Target in Alzheimer's Disease.Molecular neurobiology · 2024Review
- Ion Channel Dysregulation Following Intracerebral Hemorrhage.Neuroscience bulletin · 2024Review
- Unlocking the therapeutic potential of P2X7 receptor: a comprehensive review of its role in neurodegenerative disorders.Frontiers in pharmacology · 2024Review
- Oncomodulin regulates spontaneous calcium signalling and maturation of afferent innervation in cochlear outer hair cells.The Journal of physiology · 2023Article
- Untangling Macropore Formation and Current Facilitation in P2X7.International journal of molecular sciences · 2023Review
- Article
- Medullary astrocytes mediate irregular breathing patterns generation in chronic heart failure through purinergic P2X7 receptor signalling.EBioMedicine · 2022Article
- Using Whole-Cell Electrophysiology and Patch-Clamp Photometry to Characterize P2X7 Receptor Currents.Methods in molecular biology (Clifton, N.J.) · 2022Article
- P2X4 Receptors Mediate CaInternational journal of molecular sciences · 2021Article
- Structural basis for the functional properties of the P2X7 receptor for extracellular ATP.Purinergic signalling · 2021Review
- P2X7 Receptors and TMEM16 Channels Are Functionally Coupled with Implications for Macropore Formation and Current Facilitation.International journal of molecular sciences · 2021Article
- P2X7 receptor: a critical regulator and potential target for breast cancer.Journal of molecular medicine (Berlin, Germany) · 2021Review
- 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
- Interaction between Calcium Chelators and the Activity of P2X7 Receptors in Mouse Motor Synapses.International journal of molecular sciences · 2020Article
- Full-Length P2XCell · 2019Article
- ATP-Gated P2X7 Receptors Require Chloride Channels To Promote Inflammation in Human Macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The ATP-gated P2X(7) receptor (P2X(7)R) is a highly unusual calcium-permeable cationic channel in that within seconds of its activation, dramatic and reversible cytoskeletal rearrangements with prominent membrane blebbing occurs. Agonist-induced membrane currents at hyperpolarized potentials show pronounced facilitation during the initial 30-100 s of receptor activation but mechanisms responsible have not been elucidated. We measured facilitation of ATP-gated currents in HEK cells expressing rat P2X(7)R and delineated distinct calcium-dependent and independent processes. The calcium-dependent facilitation was composed of an instantaneous (millisecond time domain) and slowly developing (time constant, 20 s with maximum agonist stimulation) component. Both components were prevented when recording with a highly specific calmodulin (CaM) inhibitory peptide but only the instantaneous component was reduced by expression of the dominant-negative EF-handless CaM mutant. Coimmunoprecipitation assays detected low levels of CaM binding to unstimulated P2X(7)R, and this increased by 50% during 45 s stimulation of the receptor. We identified a novel 1-5-16 Ca(2+)-dependent CaM binding motif in the intracellular C terminus of P2X(7)R; mutations in this domain resulted in the absence of calcium-dependent facilitation and binding of CaM to unstimulated or stimulated receptor. Blockade of CaM binding also delayed membrane blebbing by threefold. Our results demonstrate that CaM binds constitutively to closed P2X(7)R channels and dynamically during channel activation to significantly enhance and prolong calcium entry. This is the first example of CaM deregulating, rather than tightly controlling, calcium entry through an ion channel.
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Registered trials
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.