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Cell migration and invasion are both critically dependent on changes in cell volume and shape driven by the transmembrane transport of osmotically important ions such as K<jats:sup>+<\/jats:sup> and Cl<jats:sup>\u2212<\/jats:sup>. However, while the Cl<jats:sup>\u2212<\/jats:sup> channels participating in cell volume regulation have been clearly identified, the precise nature of the K<jats:sup>+<\/jats:sup> channels involved is still uncertain. Using a combination of electrophysiological and imaging approaches in GBM U87\u2010MG cells, we found that hypotonic\u2010induced cell swelling triggered the opening of Ca<jats:sup>2+<\/jats:sup>\u2010activated K<jats:sup>+<\/jats:sup> (K<jats:sub>Ca<\/jats:sub>) channels of large and intermediate conductance (BK<jats:sub>Ca<\/jats:sub> and IK<jats:sub>Ca<\/jats:sub>, respectively), both highly expressed in GBM cells. The influx of Ca<jats:sup>2+<\/jats:sup> mediated by the hypotonic\u2010induced activation of mechanosensitive channels was found to be a key step for opening both the BK<jats:sub>Ca<\/jats:sub> and the IK<jats:sub>Ca<\/jats:sub> channels. Finally, the activation of both K<jats:sub>Ca<\/jats:sub> channels mediated by mechanosensitive channels was found to be essential for the development of the regulatory volume decrease following hypotonic shock. Taken together, these data indicate that K<jats:sub>Ca<\/jats:sub> channels are the main K<jats:sup>+<\/jats:sup> channels responsible for the volume regulation in U87\u2010MG cells.<\/jats:p>","DOI":"10.1002\/jcp.31072","type":"journal-article","created":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T10:33:33Z","timestamp":1689071613000},"page":"2120-2134","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Ca<sup>2+<\/sup>\u2010activated K<sup>+<\/sup> channels regulate cell volume in human glioblastoma cells"],"prefix":"10.1002","volume":"238","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0720-3009","authenticated-orcid":false,"given":"Antonio","family":"Michelucci","sequence":"first","affiliation":[{"name":"Department of Chemistry, Biology, and Biotechnology University of Perugia Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Sforna","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biology, and Biotechnology University of Perugia Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Di Battista","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biology, and Biotechnology University of Perugia Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Franciolini","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biology, and Biotechnology University of Perugia Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4723-0650","authenticated-orcid":false,"given":"Luigi","family":"Catacuzzeno","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biology, and Biotechnology University of Perugia Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/JBC.M002327200"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/JBC.M409708200"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/JBC.M607730200"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/PNAS.1012867108\/-\/DCSUPPLEMENTAL\/PNAS.201012867SI.PDF"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/SCIENCE.1132915"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/CELLS11172656"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/CANCERS11030307"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/FNCEL.2015.00152"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/S00232-013-9609-9"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEURON.2018.09.046"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/330066A0"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/S00401-007-0293-7"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/SCIENCE.1193270"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3171\/JNS.1998.88.1.0001"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.SONCN.2018.10.001"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/S00232-001-0115-0"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/AJPCELL.00245.2002"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000095135"},{"issue":"2","key":"e_1_2_9_20_1","first-page":"231","article-title":"The pharmacology of mechanogated membrane ion channels","volume":"48","author":"Hamill O. 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