{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T22:31:50Z","timestamp":1784932310999,"version":"3.55.0"},"reference-count":59,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T00:00:00Z","timestamp":1646006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T00:00:00Z","timestamp":1646006400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG 21558"],"award-info":[{"award-number":["IG 21558"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background and purpose<\/jats:title>\n                    <jats:p>The volume regulated anion channel (VRAC) is known to be involved in different aspects of cancer cell behaviour and response to therapies. For this reason, we investigated the effect of DCPIB, a presumably specific blocker of VRAC, in two types of cancer: pancreatic duct adenocarcinoma (PDAC) and melanoma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental approach<\/jats:title>\n                    <jats:p>\n                      We used patch\u2010clamp electrophysiology, supported by Ca\n                      <jats:sup>2+<\/jats:sup>\n                      imaging, gene expression analysis, docking simulation and mutagenesis. We employed two PDAC lines (Panc\u20101 and MiaPaCa\u20102), as well as a primary (IGR39) and a metastatic (IGR37) melanoma line.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key results<\/jats:title>\n                    <jats:p>\n                      DCPIB markedly increased whole\u2010cell currents in Panc\u20101, MiaPaca2 and IGR39, but not in IGR37 cells. The currents were mostly mediated by K\n                      <jats:sub>Ca<\/jats:sub>\n                      1.1 channels, commonly known as BK channels. We confirmed DCPIB activation of BK channels also in HEK293 cells transfected with \u03b1 subunits of this channel. Further experiments showed that in IGR39, and to a smaller degree also in Panc\u20101 cells, DCPIB induced a rapid Ca\n                      <jats:sup>2+<\/jats:sup>\n                      influx. This, in turn, indirectly potentiated BK channels and, in IGR39 cells, additionally activated other Ca\n                      <jats:sup>2+<\/jats:sup>\n                      \u2010dependent channels. However, Ca\n                      <jats:sup>2+<\/jats:sup>\n                      influx was not required for activation of BK channels by DCPIB, as such activation involved the extracellular part of the protein and we have identified a residue crucial for binding.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and implications<\/jats:title>\n                    <jats:p>\n                      DCPIB directly targeted BK channels and, also, acutely increased intracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      . Our findings extend the list of DCPIB effects that should be taken into consideration for future development of DCPIB\u2010based modulators of ion channels and other membrane proteins.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.15810","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T21:49:54Z","timestamp":1643665794000},"page":"3452-3469","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["The VRAC blocker DCPIB directly gates the BK channels and increases intracellular Ca\n                    <sup>2+<\/sup>\n                    in melanoma and pancreatic duct adenocarcinoma cell lines"],"prefix":"10.1111","volume":"179","author":[{"given":"Paolo","family":"Zuccolini","sequence":"first","affiliation":[{"name":"Institute of Biophysics National Research Council  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loretta","family":"Ferrera","sequence":"additional","affiliation":[{"name":"Institute of Biophysics National Research Council  Genoa Italy"},{"name":"U.O.C. Genetica Medica, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Remigante","sequence":"additional","affiliation":[{"name":"Institute of Biophysics National Research Council  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiana","family":"Picco","sequence":"additional","affiliation":[{"name":"Institute of Biophysics National Research Council  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Barbieri","sequence":"additional","affiliation":[{"name":"Institute of Biophysics National Research Council  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Bertelli","sequence":"additional","affiliation":[{"name":"Institute of Biophysics National Research Council  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1287-6176","authenticated-orcid":false,"given":"Oscar","family":"Moran","sequence":"additional","affiliation":[{"name":"Institute of Biophysics National Research Council  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Gavazzo","sequence":"additional","affiliation":[{"name":"Institute of Biophysics National Research Council  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8644-8847","authenticated-orcid":false,"given":"Michael","family":"Pusch","sequence":"additional","affiliation":[{"name":"Institute of Biophysics National Research Council  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,28]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.103820"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.14303"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)01096-X"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15543"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15539"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.33594\/000000329"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210036"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.112.080457"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26040785"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1515\/hsz-2019-0189"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14443"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704413"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-016-1794-9"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.10349"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-020-01151-3"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22168359"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.08.011"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2010-0190"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)83641-4"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2013.10.026"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/1758-2946-4-17"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature20775"},{"issue":"5","key":"e_1_2_12_24_1","first-page":"876","article-title":"Visual identification of individual transfected cells for electrophysiology using antibody\u2010coated beads","volume":"17","author":"Jurman M. 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