000268470 001__ 268470
000268470 005__ 20240403131604.0
000268470 0247_ $$2pmc$$apmc:PMC10895799
000268470 0247_ $$2doi$$a10.1186/s12974-024-03042-6
000268470 0247_ $$2pmid$$apmid:38409076
000268470 037__ $$aDZNE-2024-00222
000268470 041__ $$aEnglish
000268470 082__ $$a610
000268470 1001_ $$aRifat, Ali$$b0
000268470 245__ $$aDifferential contribution of THIK-1 K+ channels and P2X7 receptors to ATP-mediated neuroinflammation by human microglia.
000268470 260__ $$aLondon$$bBioMed Central$$c2024
000268470 3367_ $$2DRIVER$$aarticle
000268470 3367_ $$2DataCite$$aOutput Types/Journal article
000268470 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1710238961_4388
000268470 3367_ $$2BibTeX$$aARTICLE
000268470 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000268470 3367_ $$00$$2EndNote$$aJournal Article
000268470 520__ $$aNeuroinflammation is highly influenced by microglia, particularly through activation of the NLRP3 inflammasome and subsequent release of IL-1β. Extracellular ATP is a strong activator of NLRP3 by inducing K+ efflux as a key signaling event, suggesting that K+-permeable ion channels could have high therapeutic potential. In microglia, these include ATP-gated THIK-1 K+ channels and P2X7 receptors, but their interactions and potential therapeutic role in the human brain are unknown. Using a novel specific inhibitor of THIK-1 in combination with patch-clamp electrophysiology in slices of human neocortex, we found that THIK-1 generated the main tonic K+ conductance in microglia that sets the resting membrane potential. Extracellular ATP stimulated K+ efflux in a concentration-dependent manner only via P2X7 and metabotropic potentiation of THIK-1. We further demonstrated that activation of P2X7 was mandatory for ATP-evoked IL-1β release, which was strongly suppressed by blocking THIK-1. Surprisingly, THIK-1 contributed only marginally to the total K+ conductance in the presence of ATP, which was dominated by P2X7. This suggests a previously unknown, K+-independent mechanism of THIK-1 for NLRP3 activation. Nuclear sequencing revealed almost selective expression of THIK-1 in human brain microglia, while P2X7 had a much broader expression. Thus, inhibition of THIK-1 could be an effective and, in contrast to P2X7, microglia-specific therapeutic strategy to contain neuroinflammation.
000268470 536__ $$0G:(DE-HGF)POF4-353$$a353 - Clinical and Health Care Research (POF4-353)$$cPOF4-353$$fPOF IV$$x0
000268470 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000268470 650_2 $$2MeSH$$aHumans
000268470 650_2 $$2MeSH$$aMicroglia: metabolism
000268470 650_2 $$2MeSH$$aNLR Family, Pyrin Domain-Containing 3 Protein: metabolism
000268470 650_2 $$2MeSH$$aNeuroinflammatory Diseases
000268470 650_2 $$2MeSH$$aIon Channels: metabolism
000268470 650_2 $$2MeSH$$aAdenosine Triphosphate: pharmacology
000268470 650_2 $$2MeSH$$aAdenosine Triphosphate: metabolism
000268470 650_2 $$2MeSH$$aReceptors, Purinergic P2X7: metabolism
000268470 650_7 $$2NLM Chemicals$$aNLR Family, Pyrin Domain-Containing 3 Protein
000268470 650_7 $$2Other$$aHuman brain
000268470 650_7 $$2Other$$aIon channels
000268470 650_7 $$2Other$$aMicroglia
000268470 650_7 $$2Other$$aNeocortex
000268470 650_7 $$2Other$$aNeuroinflammation
000268470 650_7 $$2Other$$aPharmacology
000268470 650_7 $$2Other$$aPurinergic signalling
000268470 650_7 $$2NLM Chemicals$$aIon Channels
000268470 650_7 $$08L70Q75FXE$$2NLM Chemicals$$aAdenosine Triphosphate
000268470 650_7 $$2NLM Chemicals$$aReceptors, Purinergic P2X7
000268470 7001_ $$aOssola, Bernardino$$b1
000268470 7001_ $$aBürli, Roland W$$b2
000268470 7001_ $$aDawson, Lee A$$b3
000268470 7001_ $$aBrice, Nicola L$$b4
000268470 7001_ $$aRowland, Anna$$b5
000268470 7001_ $$aLizio, Marina$$b6
000268470 7001_ $$aXu, Xiao$$b7
000268470 7001_ $$aPage, Keith$$b8
000268470 7001_ $$aFidzinski, Pawel$$b9
000268470 7001_ $$aOnken, Julia$$b10
000268470 7001_ $$aHoltkamp, Martin$$b11
000268470 7001_ $$0P:(DE-2719)2812386$$aHeppner, Frank L$$b12$$udzne
000268470 7001_ $$aGeiger, Jörg R P$$b13
000268470 7001_ $$aMadry, Christian$$b14
000268470 773__ $$0PERI:(DE-600)2156455-3$$a10.1186/s12974-024-03042-6$$gVol. 21, no. 1, p. 58$$n1$$p58$$tJournal of neuroinflammation$$v21$$x1742-2094$$y2024
000268470 8564_ $$uhttps://pub.dzne.de/record/268470/files/DZNE-2024-00222%20SUP1.pdf
000268470 8564_ $$uhttps://pub.dzne.de/record/268470/files/DZNE-2024-00222%20SUP2.pdf
000268470 8564_ $$uhttps://pub.dzne.de/record/268470/files/DZNE-2024-00222.pdf$$yOpenAccess
000268470 8564_ $$uhttps://pub.dzne.de/record/268470/files/DZNE-2024-00222%20SUP1.pdf?subformat=pdfa$$xpdfa
000268470 8564_ $$uhttps://pub.dzne.de/record/268470/files/DZNE-2024-00222%20SUP2.pdf?subformat=pdfa$$xpdfa
000268470 8564_ $$uhttps://pub.dzne.de/record/268470/files/DZNE-2024-00222.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000268470 909CO $$ooai:pub.dzne.de:268470$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire
000268470 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812386$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b12$$kDZNE
000268470 9131_ $$0G:(DE-HGF)POF4-353$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vClinical and Health Care Research$$x0
000268470 9141_ $$y2024
000268470 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-10-25
000268470 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2023-10-25
000268470 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2023-10-25
000268470 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2023-10-25
000268470 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2023-10-25
000268470 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bJ NEUROINFLAMM : 2022$$d2023-10-25
000268470 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2023-10-25
000268470 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2023-04-12T15:09:06Z
000268470 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2023-04-12T15:09:06Z
000268470 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2023-10-25
000268470 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2023-10-25
000268470 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-10-25
000268470 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0
000268470 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000268470 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2023-10-25
000268470 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2023-10-25
000268470 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bJ NEUROINFLAMM : 2022$$d2023-10-25
000268470 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-10-25
000268470 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central$$d2023-10-25
000268470 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-10-25
000268470 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Anonymous peer review$$d2023-04-12T15:09:06Z
000268470 9201_ $$0I:(DE-2719)1810007$$kAG Heppner$$lNeuroimmunology$$x0
000268470 980__ $$ajournal
000268470 980__ $$aVDB
000268470 980__ $$aUNRESTRICTED
000268470 980__ $$aI:(DE-2719)1810007
000268470 9801_ $$aFullTexts