{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:56:07Z","timestamp":1790952967497,"version":"4.1.0"},"reference-count":81,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"abstract":"\n Abstract<\/jats:title>\n \n Large\u2010conductance Ca\n 2+<\/jats:sup>\n \u2010activated K\n +<\/jats:sup>\n (BK) channels regulate excitability across physiological systems, and BK channelopathies cause neurodevelopmental delay, cognitive disability and structural brain malformations. The firing rate response of CO\n 2<\/jats:sub>\n \/pH chemosensitive neurones has been suggested to be modulated by the BK channels\u2019 activity, which would function as a \u2018brake\u2019 on the chemosensitive response. Thus, our study examined the role of BK channels in ventilatory, metabolic and behavioural responses under normocapnic and hypercapnic conditions in wild\u2010type (\n \n Slo1\n +\/+<\/jats:sup>\n <\/jats:italic>\n ) and BK channel knockout (\n \n Slo1\n \u2212\/\u2212<\/jats:sup>\n <\/jats:italic>\n ) mice of both sexes during postnatal development. Additionally, the electrophysiological properties and chemosensitivity of locus coeruleus (LC) neurones in\n \n Slo1\n +\/+<\/jats:sup>\n <\/jats:italic>\n and\n \n Slo1\n \u2212\/\u2212<\/jats:sup>\n <\/jats:italic>\n mice of both sexes were studied. Our data show that\n \n Slo1\n \u2212\/\u2212<\/jats:sup>\n <\/jats:italic>\n mice displayed multiple changes in respiratory and behavioural phenotypes. Across sexes,\n \n Slo1\n \u2212\/\u2212<\/jats:sup>\n <\/jats:italic>\n animals experienced a higher rate of apnoeic events: females exhibited more spontaneous apnoeas, whereas males showed more post\u2010sigh apnoeas and sighs.\n \n Slo1\n \u2212\/\u2212<\/jats:sup>\n <\/jats:italic>\n males also demonstrated an exaggerated chewing reflex. Behaviourally,\n \n Slo1\n \u2212\/\u2212<\/jats:sup>\n <\/jats:italic>\n females spent less time in the periphery and more time in the centre of the open\u2010field arena compared with wild\u2010type females. During the panic\u2010inducing 20% CO\n 2<\/jats:sub>\n challenge, both sexes showed reduced defensive responses, including fewer escape jumps. Lastly, LC neurones from\n \n Slo1\n \u2212\/\u2212<\/jats:sup>\n <\/jats:italic>\n males exhibited an enhanced chemosensitive response to CO\n 2<\/jats:sub>\n compared with controls. These findings demonstrate that loss of BK channels disrupts respiratory stability, alters behavioural responses and enhances central CO\n 2<\/jats:sub>\n chemosensitivity in an age\u2010 and sex\u2010dependent manner.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n Absence of BK channels increases breathing variability and apnoea events during postnatal development.<\/jats:p>\n <\/jats:list-item>\n \n BK channel deletion leads to an augmented hypercapnic ventilatory response during postnatal development in a sex\u2010dependent manner.<\/jats:p>\n <\/jats:list-item>\n \n Loss of BK channels reduces panic\u2010like behavioural responses during panic attack induction.<\/jats:p>\n <\/jats:list-item>\n \n \n LC neurones lacking BK channels exhibit increased CO\n 2<\/jats:sub>\n chemosensitivity in male mice.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp291929","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:35:25Z","timestamp":1790951725000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Large\u2010conductance calcium\u2010activated potassium (BK) channels regulate respiratory, metabolic and behavioural responses to CO\n 2<\/sub>\n \/pH in mice"],"prefix":"10.1113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2328-9842","authenticated-orcid":false,"given":"Bianca","family":"de Avila\u2010Martins","sequence":"first","affiliation":[{"name":"Department of Animal Morphology and Physiology Sao Paulo State University \u2013 UNESP\/FCAV Jaboticabal S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8270-1892","authenticated-orcid":false,"given":"Luis Gustavo A.","family":"Patrone","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Institute of Biological Science Federal University of Minas Gerais \u2013 UFMG Belo Horizonte Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0571-2539","authenticated-orcid":false,"given":"Alana T.","family":"Frias","sequence":"additional","affiliation":[{"name":"Department of Animal Morphology and Physiology Sao Paulo State University \u2013 UNESP\/FCAV Jaboticabal S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabela Xavier","family":"Medalha","sequence":"additional","affiliation":[{"name":"Department of Animal Morphology and Physiology Sao Paulo State University \u2013 UNESP\/FCAV Jaboticabal S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Bernardes\u2010Ribeiro","sequence":"additional","affiliation":[{"name":"Department of Animal Morphology and Physiology Sao Paulo State University \u2013 UNESP\/FCAV Jaboticabal S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine A.","family":"Ratliff","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Cell Biology and Physiology Wright State University Boonshoft School of Medicine Dayton Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Santin","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences University of Missouri\u2010Columbia Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1180-1132","authenticated-orcid":false,"given":"K\u00eania C.","family":"B\u00edcego","sequence":"additional","affiliation":[{"name":"Department of Animal Morphology and Physiology Sao Paulo State University \u2013 UNESP\/FCAV Jaboticabal S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4097-5286","authenticated-orcid":false,"given":"Luciane H.","family":"Gargaglioni","sequence":"additional","affiliation":[{"name":"Department of Animal Morphology and Physiology Sao Paulo State University \u2013 UNESP\/FCAV Jaboticabal S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"issue":"5859","key":"e_1_2_5_2_1","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1038\/296746a0","article-title":"Intracellular Ca2+ activates a fast voltage\u2010sensitive K+ current in vertebrate sympathetic neurones","volume":"296","author":"Adams P. 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