{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T09:59:55Z","timestamp":1784627995878,"version":"3.55.0"},"reference-count":54,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2024,4,20]],"date-time":"2024-04-20T00:00:00Z","timestamp":1713571200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,9]]},"abstract":"Abstract<\/jats:title>Macrophages (M\u03a6) play pivotal roles in tissue homeostasis and repair. Their mechanical environment has been identified as a key modulator of various cell functions, and M\u03a6 mechanosensitivity is likely to be critical \u2013 in particular in a rhythmically contracting organ such as the heart. Cultured M\u03a6, differentiated in vitro<\/jats:italic> from bone marrow (M\u03a6BM<\/jats:sub>), form a popular research model. This study explores the activity of mechanosensitive ion channels (MSC) in murine M\u03a6BM<\/jats:sub> and compares it to MSC activity in M\u03a6 enzymatically isolated from cardiac tissue (tissue\u2010resident M\u03a6; M\u03a6TR<\/jats:sub>). We show that M\u03a6BM<\/jats:sub> and M\u03a6TR<\/jats:sub> have stretch\u2010induced currents, indicating the presence of functional MSC in their plasma membrane. The current profiles in M\u03a6BM<\/jats:sub> and in M\u03a6TR<\/jats:sub> show characteristics of cation non\u2010selective MSC such as Piezo1 or transient receptor potential channels. While Piezo1 ion channel activity is detectable in the plasma membrane of M\u03a6BM<\/jats:sub> using the patch\u2010clamp technique, or by measuring cytosolic calcium concentration upon perfusion with the Piezo1 channel agonist Yoda1, no Piezo1 channel activity was observed in M\u03a6TR<\/jats:sub>. The selective transient receptor potential vanilloid 4 (TRPV4) channel agonist GSK1016790A induces calcium entry in M\u03a6TR<\/jats:sub> and in M\u03a6BM<\/jats:sub>. In M\u03a6 isolated from left\u2010ventricular scar tissue 28\u00a0days after cryoablation, stretch\u2010induced current characteristics are not significantly different compared to non\u2010injured control tissue, even though scarred ventricular tissue is expected to be mechanically remodelled and to contain an altered composition of pre\u2010existing cardiac and circulation\u2010recruited M\u03a6. Our data suggest that the in vitro<\/jats:italic> differentiation protocols used to obtain M\u03a6BM<\/jats:sub> generate cells that differ from M\u03a6 recruited from the circulation during tissue repair in vivo<\/jats:italic>. Further investigations are needed to explore MSC identity in lineage\u2010traced M\u03a6 in scar tissue, and to compare mechanosensitivity of circulating monocytes with that of M\u03a6BM<\/jats:sub>.\nimage<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>Key points<\/jats:title>\nBone marrow\u2010derived (M\u03a6BM<\/jats:sub>) and tissue resident (M\u03a6TR<\/jats:sub>) macrophages have stretch\u2010induced currents, indicating expression of functional mechanosensitive channels (MSC) in their plasma membrane.<\/jats:p><\/jats:list-item>\nStretch\u2010activated current profiles show characteristics of cation non\u2010selective MSC; and mRNA coding for MSC, including Piezo1 and TRPV4, is expressed in murine M\u03a6BM<\/jats:sub> and in M\u03a6TR<\/jats:sub>.<\/jats:p><\/jats:list-item>\nCalcium entry upon pharmacological activation of TRPV4 confirms functionality of the channel in M\u03a6TR<\/jats:sub> and in M\u03a6BM<\/jats:sub>.<\/jats:p><\/jats:list-item>\nPiezo1 ion channel activity is detected in the plasma membrane of M\u03a6BM<\/jats:sub> but not in M\u03a6TR<\/jats:sub>, suggesting that M\u03a6BM<\/jats:sub> may not be a good model to study the mechanotransduction of M\u03a6TR<\/jats:sub>.<\/jats:p><\/jats:list-item>\nStretch\u2010induced currents, Piezo1\u00a0mRNA expression and response to pharmacological activation are not significantly changed in cardiac M\u03a6 28\u00a0days after cryoinjury compared to sham operated mice.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp284805","type":"journal-article","created":{"date-parts":[[2024,4,20]],"date-time":"2024-04-20T13:15:00Z","timestamp":1713618900000},"page":"4437-4456","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Piezo1 stretch\u2010activated channel activity differs between murine bone marrow\u2010derived and cardiac tissue\u2010resident macrophages"],"prefix":"10.1113","volume":"602","author":[{"given":"Ana","family":"Simon\u2010Chica","sequence":"first","affiliation":[{"name":"Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg \u2013 Bad Krozingen, Medical Center \u2013 University of Freiburg and Faculty of Medicine University of Freiburg Freiburg Germany"},{"name":"Centro Nacional de Investigaciones Cardiovasculares Carlos III Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8893-8287","authenticated-orcid":false,"given":"Alexander","family":"Klesen","sequence":"additional","affiliation":[{"name":"Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg \u2013 Bad Krozingen, Medical Center \u2013 University of Freiburg and Faculty of Medicine University of Freiburg Freiburg Germany"},{"name":"Department of Congenital Heart Defects and Paediatric Cardiology, University Heart Center Freiburg \u2013 Bad Krozingen, Medical Center \u2013 University of Freiburg and Faculty of Medicine University of Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1832-6976","authenticated-orcid":false,"given":"Ramona","family":"Emig","sequence":"additional","affiliation":[{"name":"Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg \u2013 Bad Krozingen, Medical Center \u2013 University of Freiburg and Faculty of Medicine University of Freiburg Freiburg Germany"},{"name":"Centre for Integrative Biological Signalling Studies (CIBSS), Faculty of Biology University of Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1170-8085","authenticated-orcid":false,"given":"Andy","family":"Chan","sequence":"additional","affiliation":[{"name":"W\u00fcrzburg Institute of Systems Immunology Max Planck Research Group at Julius\u2010Maximilians\u2010University W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Greiner","sequence":"additional","affiliation":[{"name":"Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg \u2013 Bad Krozingen, Medical Center \u2013 University of Freiburg and Faculty of Medicine University of Freiburg Freiburg Germany"},{"name":"Centre for Integrative Biological Signalling Studies (CIBSS), Faculty of Biology University of Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3364-5898","authenticated-orcid":false,"given":"Dominic","family":"Gr\u00fcn","sequence":"additional","affiliation":[{"name":"W\u00fcrzburg Institute of Systems Immunology Max Planck Research Group at Julius\u2010Maximilians\u2010University W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9107-5558","authenticated-orcid":false,"given":"Achim","family":"Lother","sequence":"additional","affiliation":[{"name":"Interdisciplinary Medical Intensive Care, Medical Center \u2013 University of Freiburg and Faculty of Medicine University of Freiburg Freiburg Germany"},{"name":"Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine University of Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Hilgendorf","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology, University Heart Center Freiburg \u2013 Bad Krozingen, Medical Center \u2013 University of Freiburg and Faculty of Medicine University of Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva A.","family":"Rog\u2010Zielinska","sequence":"additional","affiliation":[{"name":"Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg \u2013 Bad Krozingen, Medical Center \u2013 University of Freiburg and Faculty of Medicine University of Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3813-3127","authenticated-orcid":false,"given":"Ursula","family":"Ravens","sequence":"additional","affiliation":[{"name":"Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg \u2013 Bad Krozingen, Medical Center \u2013 University of Freiburg and Faculty of Medicine University of Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0416-6270","authenticated-orcid":false,"given":"Peter","family":"Kohl","sequence":"additional","affiliation":[{"name":"Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg \u2013 Bad Krozingen, Medical Center \u2013 University of Freiburg and Faculty of Medicine University of Freiburg Freiburg Germany"},{"name":"Centre for Integrative Biological Signalling Studies (CIBSS), Faculty of Biology University of Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5873-9436","authenticated-orcid":false,"given":"Franziska","family":"Schneider\u2010Warme","sequence":"additional","affiliation":[{"name":"Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg \u2013 Bad Krozingen, Medical Center \u2013 University of Freiburg and Faculty of Medicine University of Freiburg Freiburg Germany"},{"name":"Centre for Integrative Biological Signalling Studies (CIBSS), Faculty of Biology University of Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5708-6410","authenticated-orcid":false,"given":"R\u00e9mi","family":"Peyronnet","sequence":"additional","affiliation":[{"name":"Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg \u2013 Bad Krozingen, Medical Center \u2013 University of Freiburg and Faculty of Medicine University of Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky379"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23482-5"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0059-x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.045536"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.01.033"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.313348"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau0964"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.09.046"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.07.001"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.570195"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12551-021-00838-1"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.11.019"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-0830-2_17"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201808050"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/28.8.1193"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11020233"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.303567"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.03.050"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2021.05.002"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21178-4"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/2211-5463.12896"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.1044729"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12364"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.120.16629"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.816149"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2020.11.004"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.056424"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00413"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.031"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.238360"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-022-01663-4"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.11.030"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.305043"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-00306-w"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-023-02974-1"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01273"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501688"},{"key":"e_1_2_6_40_1","unstructured":"Schmidt U. Weigert M. Broaddus C. &Myers G.(2018). Cell detection with star\u2010convex polygons. Medical Image Computing and Computer Assisted Intervention\u2013MICCAI 2018: 21st International Conference Granada Spain September 16\u201320 2018 Proceedings Part II 11 Springer."},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.970234"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvab126"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1485-8"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-020-01018-x"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2009.05.018"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.07369"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1149336"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1080\/19336950.2021.1923199"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M304388200"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200910334"},{"key":"e_1_2_6_51_1","doi-asserted-by":"crossref","unstructured":"Weischenfeldt J. &Porse B.(2008).Bone marrow\u2010derived macrophages (BMM): Isolation and applications. CSH Protoc.https:\/\/doi.org\/10.1101\/pdb.prot5080","DOI":"10.1101\/pdb.prot5080"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.07.003"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2022.08.023"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44161-022-00082-0"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.766416"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP284805","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,16]],"date-time":"2024-11-16T15:29:18Z","timestamp":1731770958000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP284805"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,20]]},"references-count":54,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1113\/JP284805"],"URL":"https:\/\/doi.org\/10.1113\/jp284805","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,20]]},"assertion":[{"value":"2023-04-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}