XB-ART-57882
Int J Mol Sci
2020 Nov 11;2122:. doi: 10.3390/ijms21228489.
Show Gene links
Show Anatomy links
Dissection of P2X4 and P2X7 Receptor Current Components in BV-2 Microglia.
Trang M
,
Schmalzing G
,
Müller CE
,
Markwardt F
.
???displayArticle.abstract???
Microglia cells represent the immune system of the central nervous system. They become activated by ATP released from damaged and inflamed tissue via purinergic receptors. Ionotropic purinergic P2X4 and P2X7 receptors have been shown to be involved in neurological inflammation and pain sensation. Whether the two receptors assemble exclusively as homotrimers or also as heterotrimers is still a matter of debate. We investigated the expression of P2X receptors in BV-2 microglia cells applying the whole-cell voltage-clamp technique. We dissected P2X4 and P2X7 receptor-mediated current components by using specific P2X4 and P2X7 receptor blockers and by their characteristic current kinetics. We found that P2X4 and P2X7 receptors are activated independently from each other, indicating that P2X4/P2X7 heteromers are not of functional significance in these cells. The pro-inflammatory mediators lipopolysaccharide and interferon γ, if applied in combination, upregulated P2X4, but not P2X7 receptor-dependent current components also arguing against phenotypically relevant heteromerization of P2X4 and P2X7 receptor subunits.
???displayArticle.pubmedLink??? 33187309
???displayArticle.link??? Int J Mol Sci
???displayArticle.grants??? [+]
Schm 536/9-2 Deutsche Forschungsgemeinschaft, MA 1581/15-2 Deutsche Forschungsgemeinschaft
Species referenced: Xenopus laevis
Genes referenced: p2rx4 p2rx7
GO keywords: microglial cell activation
???attribute.lit??? ???displayArticles.show???
References [+] :
Adriouch,
Cutting edge: a natural P451L mutation in the cytoplasmic domain impairs the function of the mouse P2X7 receptor.
2002, Pubmed
Adriouch, Cutting edge: a natural P451L mutation in the cytoplasmic domain impairs the function of the mouse P2X7 receptor. 2002, Pubmed
Allsopp, Mapping the Allosteric Action of Antagonists A740003 and A438079 Reveals a Role for the Left Flipper in Ligand Sensitivity at P2X7 Receptors. 2018, Pubmed
Bernier, Purinergic regulation of inflammasome activation after central nervous system injury. 2012, Pubmed
Bertin, Increased surface P2X4 receptor regulates anxiety and memory in P2X4 internalization-defective knock-in mice. 2021, Pubmed
Bhattacharya, The microglial ATP-gated ion channel P2X7 as a CNS drug target. 2016, Pubmed
Bianchi, Pharmacological characterization of recombinant human and rat P2X receptor subtypes. 1999, Pubmed , Xenbase
Bianco, A role for P2X7 in microglial proliferation. 2006, Pubmed
Bianco, Pathophysiological roles of extracellular nucleotides in glial cells: differential expression of purinergic receptors in resting and activated microglia. 2005, Pubmed
Bobanovic, P2X receptor trafficking in neurons is subunit specific. 2002, Pubmed
Bobinski, Interleukin-4 mediates the analgesia produced by low-intensity exercise in mice with neuropathic pain. 2018, Pubmed
Boumechache, Analysis of assembly and trafficking of native P2X4 and P2X7 receptor complexes in rodent immune cells. 2009, Pubmed
Bretschneider, Nonselective cationic currents elicited by extracellular ATP in human B-lymphocytes. 1995, Pubmed
Brône, P2X currents in peritoneal macrophages of wild type and P2X4 -/- mice. 2007, Pubmed
Burnstock, P2X ion channel receptors and inflammation. 2016, Pubmed
Burow, Activation of ATP secretion via volume-regulated anion channels by sphingosine-1-phosphate in RAW macrophages. 2015, Pubmed
Carrillo-de Sauvage, Potent and multiple regulatory actions of microglial glucocorticoid receptors during CNS inflammation. 2013, Pubmed
Casas-Pruneda, Functional interactions between P2X4 and P2X7 receptors from mouse salivary epithelia. 2009, Pubmed
Chessell, Disruption of the P2X7 purinoceptor gene abolishes chronic inflammatory and neuropathic pain. 2005, Pubmed
Choi, Modulation of the purinergic P2X7 receptor attenuates lipopolysaccharide-mediated microglial activation and neuronal damage in inflamed brain. 2007, Pubmed
Coddou, Activation and regulation of purinergic P2X receptor channels. 2011, Pubmed
Di Virgilio, The Elusive P2X7 Macropore. 2018, Pubmed
Eggen, Microglial phenotype and adaptation. 2013, Pubmed
ElAli, Microglia Ontology and Signaling. 2016, Pubmed
Ferrari, ATP-mediated cytotoxicity in microglial cells. 1997, Pubmed
Fois, P2X4 receptor re-sensitization depends on a protonation/deprotonation cycle mediated by receptor internalization and recycling. 2018, Pubmed
Giuliani, Extracellular nucleotides and nucleosides as signalling molecules. 2019, Pubmed
Gloor, A vector for the synthesis of cRNAs encoding Myc epitope-tagged proteins in Xenopus laevis oocytes. 1995, Pubmed , Xenbase
Grudzien-Nogalska, Synthesis of anti-reverse cap analogs (ARCAs) and their applications in mRNA translation and stability. 2007, Pubmed
Guo, Evidence for functional P2X4/P2X7 heteromeric receptors. 2007, Pubmed
Guo, Expression of P2X4 receptor by lesional activated microglia during formalin-induced inflammatory pain. 2005, Pubmed
He, The role of microglial P2X7: modulation of cell death and cytokine release. 2017, Pubmed
Inoue, ATP receptors in pain sensation: Involvement of spinal microglia and P2X(4) receptors. 2005, Pubmed
Inoue, Microglia in neuropathic pain: cellular and molecular mechanisms and therapeutic potential. 2018, Pubmed
Inoue, Role of the P2X4 receptor in neuropathic pain. 2019, Pubmed
Jacob, Purinergic signaling in inflammatory cells: P2 receptor expression, functional effects, and modulation of inflammatory responses. 2013, Pubmed
Janks, ATP-Gated P2X7 Receptors Require Chloride Channels To Promote Inflammation in Human Macrophages. 2019, Pubmed
Janks, A central role for P2X7 receptors in human microglia. 2018, Pubmed
Jones, Functional characterization of the P2X(4) receptor orthologues. 2000, Pubmed
Kaiser, Lack of functional P2X7 receptor aggravates brain edema development after middle cerebral artery occlusion. 2016, Pubmed
Kessler, Expression and functional characterization of P2X receptors in mouse alveolar macrophages. 2011, Pubmed
Kettenmann, Physiology of microglia. 2011, Pubmed
Khakh, Neuromodulation by extracellular ATP and P2X receptors in the CNS. 2012, Pubmed
Klapperstück, Functional evidence of distinct ATP activation sites at the human P2X(7) receptor. 2001, Pubmed , Xenbase
Klapperstück, Characteristics of P2X7 receptors from human B lymphocytes expressed in Xenopus oocytes. 2000, Pubmed , Xenbase
Kuehnel, Sphingosine-1-phosphate receptors stimulate macrophage plasma-membrane actin assembly via ADP release, ATP synthesis and P2X7R activation. 2009, Pubmed
Kurpius, Purines induce directed migration and rapid homing of microglia to injured pyramidal neurons in developing hippocampus. 2007, Pubmed
Li, Subtype-specific control of P2X receptor channel signaling by ATP and Mg2+. 2013, Pubmed
Lively, Microglia Responses to Pro-inflammatory Stimuli (LPS, IFNγ+TNFα) and Reprogramming by Resolving Cytokines (IL-4, IL-10). 2018, Pubmed
Marchand, Role of the immune system in chronic pain. 2005, Pubmed
Masuch, Mechanism of microglia neuroprotection: Involvement of P2X7, TNFα, and valproic acid. 2016, Pubmed
McLarnon, Upregulated expression of purinergic P2X(7) receptor in Alzheimer disease and amyloid-beta peptide-treated microglia and in peptide-injected rat hippocampus. 2006, Pubmed
Mongin, Volume-regulated anion channel--a frenemy within the brain. 2016, Pubmed
Monif, Microglia: proliferation and activation driven by the P2X7 receptor. 2010, Pubmed
Murana, ATP release during cell swelling activates a Ca2+-dependent Cl- current by autocrine mechanism in mouse hippocampal microglia. 2017, Pubmed
Naemsch, P2X(4) purinoceptors mediate an ATP-activated, non-selective cation current in rabbit osteoclasts. 1999, Pubmed
Nelson, Structure-activity relationship studies on a series of novel, substituted 1-benzyl-5-phenyltetrazole P2X7 antagonists. 2006, Pubmed
North, Molecular physiology of P2X receptors. 2002, Pubmed
Papageorgiou, TLR4-activated microglia require IFN-γ to induce severe neuronal dysfunction and death in situ. 2016, Pubmed
Parisi, M1 and M2 Functional Imprinting of Primary Microglia: Role of P2X7 Activation and miR-125b. 2016, Pubmed
Persson, Contribution of sodium channels to lamellipodial protrusion and Rac1 and ERK1/2 activation in ATP-stimulated microglia. 2014, Pubmed
Prinz, Microglia in the CNS: immigrants from another world. 2011, Pubmed
Pérez-Flores, The P2X7/P2X4 interaction shapes the purinergic response in murine macrophages. 2015, Pubmed
Qureshi, Regulation of P2X4 receptors by lysosomal targeting, glycan protection and exocytosis. 2007, Pubmed
Raouf, Differential regulation of microglial P2X4 and P2X7 ATP receptors following LPS-induced activation. 2007, Pubmed
Saul, Heteromeric assembly of P2X subunits. 2013, Pubmed
Schneider, Interaction of Purinergic P2X4 and P2X7 Receptor Subunits. 2017, Pubmed , Xenbase
Schubert, Multiple ligand-ion solutions: a guide for solution preparation and computer program understanding. 1996, Pubmed
Seyffert, Dissecting individual current components of co-expressed human P2X1 and P2X7 receptors. 2004, Pubmed , Xenbase
Sim, P2X1 and P2X4 receptor currents in mouse macrophages. 2007, Pubmed
Soto, P2X4: an ATP-activated ionotropic receptor cloned from rat brain. 1996, Pubmed , Xenbase
Sperlágh, Purinergic modulation of microglial cell activation. 2007, Pubmed
Stokes, Dynamic regulation of the P2X4 receptor in alveolar macrophages by phagocytosis and classical activation. 2009, Pubmed
Stokes, Rab5 regulates internalisation of P2X4 receptors and potentiation by ivermectin. 2013, Pubmed
Stokes, P2X4 Receptor Function in the Nervous System and Current Breakthroughs in Pharmacology. 2017, Pubmed
Stolz, Homodimeric anoctamin-1, but not homodimeric anoctamin-6, is activated by calcium increases mediated by the P2Y1 and P2X7 receptors. 2015, Pubmed , Xenbase
Stoop, Different sensitivities to pH of ATP-induced currents at four cloned P2X receptors. 1997, Pubmed
Sun, Role of interleukin-4, the chemokine CCL3 and its receptor CCR5 in neuropathic pain. 2016, Pubmed
Surprenant, The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7). 1996, Pubmed
Teixeira, Diabetes-induced Neuropathic Mechanical Hyperalgesia Depends on P2X4 Receptor Activation in Dorsal Root Ganglia. 2019, Pubmed
Toulme, P2X4 receptors in activated C8-B4 cells of cerebellar microglial origin. 2010, Pubmed
Tsuda, P2 receptors, microglial cytokines and chemokines, and neuropathic pain. 2017, Pubmed
Tsuda, Microglial regulation of neuropathic pain. 2013, Pubmed
Tsuda, P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. 2003, Pubmed
Turola, Microglial microvesicle secretion and intercellular signaling. 2012, Pubmed
Verderio, ATP mediates calcium signaling between astrocytes and microglial cells: modulation by IFN-gamma. 2001, Pubmed
Verma, Deletion of the P2X4 receptor is neuroprotective acutely, but induces a depressive phenotype during recovery from ischemic stroke. 2017, Pubmed
Visentin, Two different ionotropic receptors are activated by ATP in rat microglia. 1999, Pubmed
Vázquez-Villoldo, P2X4 receptors control the fate and survival of activated microglia. 2014, Pubmed
Walhout, GATEWAY recombinational cloning: application to the cloning of large numbers of open reading frames or ORFeomes. 2000, Pubmed
Williams, Antibodies binding the head domain of P2X4 inhibit channel function and reverse neuropathic pain. 2019, Pubmed
Xu, Extracellular ATP enhances radiation-induced brain injury through microglial activation and paracrine signaling via P2X7 receptor. 2015, Pubmed
Zabala, P2X4 receptor controls microglia activation and favors remyelination in autoimmune encephalitis. 2018, Pubmed
Zhang, The role and pharmacological properties of the P2X7 receptor in neuropathic pain. 2020, Pubmed
Zhang, Dexamethasone attenuates early expression of three molecules associated with microglia/macrophages activation following rat traumatic brain injury. 2007, Pubmed