{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T16:10:31Z","timestamp":1777651831203,"version":"3.51.4"},"reference-count":63,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T00:00:00Z","timestamp":1714089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E26\/201.261\/2022"],"award-info":[{"award-number":["E26\/201.261\/2022"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E\u201026\/010\/001333\/2019"],"award-info":[{"award-number":["E\u201026\/010\/001333\/2019"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Ischaemic heart disease remains a significant cause of mortality globally. A pharmacological agent that protects cardiac mitochondria against oxygen deprivation injuries is welcome in therapy against acute myocardial infarction. Here, we evaluate the effect of large\u2010conductance Ca<jats:sup>2+<\/jats:sup>\u2010activated K<jats:sup>+<\/jats:sup> channels (BKCa) activator, Compound Z, in isolated mitochondria under hypoxia and reoxygenation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mitochondria from mice hearts were obtained by differential centrifugation. The isolated mitochondria were incubated with a BKCa channel activator, Compound Z, and subjected to normoxia or hypoxia\/reoxygenation. Mitochondrial function was evaluated by measurement of O<jats:sub>2<\/jats:sub> consumption in the complexes I, II, and IV in the respiratory states 1, 2, 3, and by maximal uncoupled O<jats:sub>2<\/jats:sub> uptake, ATP production, ROS production, transmembrane potential, and calcium retention capacity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Incubation of isolated mitochondria with Compound Z under normoxia conditions reduced the mitochondrial functions and induced the production of a significant amount of ROS. However, under hypoxia\/reoxygenation, the Compound Z prevented a profound reduction in mitochondrial functions, including reducing ROS production over the hypoxia\/reoxygenation group. Furthermore, hypoxia\/reoxygenation induced a large mitochondria depolarization, which Compound Z incubation prevented, but, even so, Compound Z created a small depolarization. The mitochondrial calcium uptake was prevented by the BKCa activator, extruding the mitochondrial calcium present before Compound Z incubation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The Compound Z acts as a mitochondrial BKCa channel activator and can protect mitochondria function against hypoxia\/reoxygenation injury, by handling mitochondrial calcium and transmembrane potential.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.14151","type":"journal-article","created":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T06:54:20Z","timestamp":1714200860000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A potent and selective activator of large\u2010conductance Ca<sup>2+<\/sup>\u2010activated K<sup>+<\/sup> channels induces preservation of mitochondrial function after hypoxia and reoxygenation by handling of calcium and transmembrane potential"],"prefix":"10.1111","volume":"240","author":[{"given":"Itanna Isis Araujo","family":"de Souza","sequence":"first","affiliation":[{"name":"Instituto de Biof\u00edsica Carlos Chagas Filho Universidade Federal do Rio de Janeiro  Rio de Janeiro Brasil"},{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o Em Cardiologia Universidade Federal do Rio de Janeiro  Rio de Janeiro Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thais","family":"da Silva\u00a0Barenco","sequence":"additional","affiliation":[{"name":"Instituto de Biof\u00edsica Carlos Chagas Filho Universidade Federal do Rio de Janeiro  Rio de Janeiro Brasil"},{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o Em Cardiologia Universidade Federal do Rio de Janeiro  Rio de Janeiro Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Eduarda Maciel Fernandes","family":"Pavarino","sequence":"additional","affiliation":[{"name":"Instituto de Biof\u00edsica Carlos Chagas Filho Universidade Federal do Rio de Janeiro  Rio de Janeiro Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcos Tadeu","family":"Couto","sequence":"additional","affiliation":[{"name":"Instituto Federal de Educa\u00e7\u00e3o Ci\u00eancia e Tecnologia do Rio de Janeiro  Rio de Janeiro Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel Oliveira","family":"de Resende","sequence":"additional","affiliation":[{"name":"Instituto Federal de Educa\u00e7\u00e3o Ci\u00eancia e Tecnologia do Rio de Janeiro  Rio de Janeiro Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dahienne Ferreira","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Instituto de Bioqu\u00edmica M\u00e9dica Leopoldo De Meis Universidade Federal do Rio de Janeiro  Duque de Caxias Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristiano Gonsalves","family":"Ponte","sequence":"additional","affiliation":[{"name":"Instituto Federal de Educa\u00e7\u00e3o Ci\u00eancia e Tecnologia do Rio de Janeiro  Rio de Janeiro Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Hamilton Matheus","family":"Nascimento","sequence":"additional","affiliation":[{"name":"Instituto de Biof\u00edsica Carlos Chagas Filho Universidade Federal do Rio de Janeiro  Rio de Janeiro Brasil"},{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o Em Cardiologia Universidade Federal do Rio de Janeiro  Rio de Janeiro Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1168-8926","authenticated-orcid":false,"given":"Leonardo","family":"Maciel","sequence":"additional","affiliation":[{"name":"Instituto de Biof\u00edsica Carlos Chagas Filho Universidade Federal do Rio de Janeiro  Rio de Janeiro Brasil"},{"name":"Universidade Federal do Rio de Janeiro  Duque de Caxias Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,4,26]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-020-0403-y"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2017.09.015"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-023-01003-3"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.305348"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.122.321582"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22063224"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00580.2022"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1413579"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1413534"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2015.00104"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1302028110"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1373909"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/35038011"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00354.2014"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.0496"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1074360"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00763.2005"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2013.03.018"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.11.035"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00198.2007"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1159\/000149790"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.111.075853"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199404000-00037"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(94)90442-1"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.07.057"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.118786"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1994.tb17171.x"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb15163.x"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13351"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.87.6.460"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000158497.09626.3b"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00434.2001"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI13200"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000181171.65293.65"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.074476"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/164_2016_79"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00032.2008"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1213\/ane.0b013e318160650f"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e318137991d"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2005.09.008"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2004.09.012"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2007.05.008"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00021.2013"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2014.03.004"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.12.1.63"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2010.01.005"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(92)81630-2"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0014-2999(96)00540-7"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2022.04.005"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.04.110"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00144a011"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26113233"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.310820"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1124\/pharmrev.121.000348"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-017-0641-2"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2023.1173462"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00545"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.5114\/aoms.2016.61789"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.748261"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2008.06.013"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20081386"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1042\/bse0470053"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0b013e31822b0bd4"}],"container-title":["Acta Physiologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apha.14151","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T07:12:56Z","timestamp":1716189176000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apha.14151"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,26]]},"references-count":63,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1111\/apha.14151"],"URL":"https:\/\/doi.org\/10.1111\/apha.14151","archive":["Portico"],"relation":{},"ISSN":["1748-1708","1748-1716"],"issn-type":[{"value":"1748-1708","type":"print"},{"value":"1748-1716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,26]]},"assertion":[{"value":"2023-10-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14151"}}