{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T18:40:55Z","timestamp":1755801655816,"version":"3.44.0"},"reference-count":51,"publisher":"American Physiological Society","issue":"6","funder":[{"name":"European Union Interreg VA Health & Life Science Programme administered by SEUPB","award":["INT-VA\/045"],"award-info":[{"award-number":["INT-VA\/045"]}]},{"name":"Research Office Dundalk Institute of Technology"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2018,12,1]]},"abstract":"<jats:p>Airway smooth muscle expresses abundant BK<jats:sub>Ca<\/jats:sub>channels, but their role in regulating contractions remains controversial. This study examines the effects of two potent BK<jats:sub>Ca<\/jats:sub>channel openers on agonist-induced phasic contractions in rabbit and mouse bronchi. First, we demonstrated the ability of 10 \u03bcM GoSlo-SR5-130 to activate BK<jats:sub>Ca<\/jats:sub>channels in inside-out patches from rabbit bronchial myocytes, where it shifted the activation V<jats:sub>1\/2<\/jats:sub>by \u221288\u2009\u00b1\u200911 mV (100 nM Ca<jats:sup>2+<\/jats:sup>, n = 7). In mouse airway smooth muscle cells, GoSlo-SR5-130 dose dependently shifted V<jats:sub>1\/2<\/jats:sub>by 12\u201383 mV over a concentration range of 1\u201330 \u03bcM. Compound X, a racemic mixture of two enantiomers, reported to be potent BK<jats:sub>Ca<\/jats:sub>channel openers, shifted V<jats:sub>1\/2<\/jats:sub>by 20\u201379 mV over a concentration range of 0.3\u20133 \u03bcM. In rabbit bronchial rings, exposure to histamine (1 \u03bcM) induced phasic contractions after a delay of ~35 min. These were abolished by GoSlo-SR5-130 (30 \u03bcM). Nifedipine (100 nM) and CaCC<jats:sub>inh<\/jats:sub>A01 (10 \u03bcM), a TMEM16A blocker, also abolished histamine-induced phasic contractions. In mouse bronchi, similar phasic contractions were evoked by exposure to U46619 (100 nM) and carbachol (100 nM). In each case, these were inhibited by concentrations of GoSlo-SR5-130 and compound X that shifted the activation V<jats:sub>1\/2<\/jats:sub>of BK<jats:sub>Ca<\/jats:sub>channels in the order of \u221280 mV. In conclusion, membrane potential-dependent regulation of L-type Ca<jats:sup>2+<\/jats:sup>channels appears to be important for histamine-, U46619-, and carbachol-induced phasic contractions in airway smooth muscle. Contractions can be abolished by BK<jats:sub>Ca<\/jats:sub>channel openers, suggesting that these channels are potential targets for treating some causes of airway obstruction.<\/jats:p>","DOI":"10.1152\/ajpcell.00068.2018","type":"journal-article","created":{"date-parts":[[2018,9,26]],"date-time":"2018-09-26T17:09:17Z","timestamp":1537981757000},"page":"C818-C829","source":"Crossref","is-referenced-by-count":7,"title":["Inhibitory effects of openers of large-conductance Ca<sup>2+<\/sup>-activated K<sup>+<\/sup>channels on agonist-induced phasic contractions in rabbit and mouse bronchial smooth muscle"],"prefix":"10.1152","volume":"315","author":[{"given":"Eamonn","family":"Bradley","sequence":"first","affiliation":[{"name":"Smooth Muscle Research Centre, Dundalk Institute of Technology, Dundalk, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roddy J.","family":"Large","sequence":"additional","affiliation":[{"name":"Smooth Muscle Research Centre, Dundalk Institute of Technology, Dundalk, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viktoriia Volodymyrivna","family":"Bihun","sequence":"additional","affiliation":[{"name":"Smooth Muscle Research Centre, Dundalk Institute of Technology, Dundalk, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas D.","family":"Mullins","sequence":"additional","affiliation":[{"name":"Smooth Muscle Research Centre, Dundalk Institute of Technology, Dundalk, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A.","family":"Hollywood","sequence":"additional","affiliation":[{"name":"Smooth Muscle Research Centre, Dundalk Institute of Technology, Dundalk, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerard P.","family":"Sergeant","sequence":"additional","affiliation":[{"name":"Smooth Muscle Research Centre, Dundalk Institute of Technology, Dundalk, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith D.","family":"Thornbury","sequence":"additional","affiliation":[{"name":"Smooth Muscle Research Centre, Dundalk Institute of Technology, Dundalk, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1985.tb17380.x"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00112606"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1006\/pulp.1994.1023"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13201"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00034.2013"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(90)90019-C"},{"key":"B7","first-page":"228","volume":"263","author":"Cheng JB","year":"1983","journal-title":"Arch Int Pharmacodyn Ther"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/PL00005141"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(85)90632-0"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-017-2028-5"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00068.2013"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1014350"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/BF00656997"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00025.2017"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00273.2015"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1164\/arrd.1983.127.5.549"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(93)90817-2"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1997.272.6.C1757"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00452.2001"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00068508"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-7-123"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1992.sp019224"},{"key":"B23","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/S0022-3565(25)22919-6","volume":"255","author":"Jones TR","year":"1990","journal-title":"J Pharmacol Exp Ther"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1080\/19336950.2016.1213930"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1991.261.6.C1204"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.22.11051"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116969"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2002-0197OC"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1995.268.2.L221"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/341152a0"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13085"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-11-138"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb16387.x"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1986.sp016000"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.33549\/physiolres.933317"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5236.633"},{"key":"B37","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/S0022-3565(24)37674-8","volume":"286","author":"Patel HJ","year":"1998","journal-title":"J Pharmacol Exp Ther"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2008.09.006"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1124\/mol.111.075853"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2014.01.035"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201200321"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-7167com"},{"key":"B43","first-page":"870","volume":"12","author":"Schoenmakers TJ","year":"1992","journal-title":"Biotechniques"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn168"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.204347"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.05.053"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1400555112"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200104000-00024"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201207-1303OC"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M800447200"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.067546"}],"container-title":["American Journal of Physiology-Cell Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpcell.00068.2018","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T15:54:30Z","timestamp":1755705270000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpcell.00068.2018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,1]]},"references-count":51,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,12,1]]}},"alternative-id":["10.1152\/ajpcell.00068.2018"],"URL":"https:\/\/doi.org\/10.1152\/ajpcell.00068.2018","relation":{},"ISSN":["0363-6143","1522-1563"],"issn-type":[{"type":"print","value":"0363-6143"},{"type":"electronic","value":"1522-1563"}],"subject":[],"published":{"date-parts":[[2018,12,1]]}}}