{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T11:57:58Z","timestamp":1784030278944,"version":"3.55.0"},"reference-count":44,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100003621","name":"Ministry of Science, ICT and Future Planning","doi-asserted-by":"publisher","award":["NRF-2021R1A2C2007243"],"award-info":[{"award-number":["NRF-2021R1A2C2007243"]}],"id":[{"id":"10.13039\/501100003621","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003624","name":"Ministry of Agriculture, Food and Rural Affairs","doi-asserted-by":"publisher","award":["317070\u20134"],"award-info":[{"award-number":["317070\u20134"]}],"id":[{"id":"10.13039\/501100003624","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003668","name":"Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003668","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002582","name":"Gwangju Institute of Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002582","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2022,7]]},"DOI":"10.1016\/j.ejphar.2022.175055","type":"journal-article","created":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T22:07:52Z","timestamp":1653602872000},"page":"175055","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"C","title":["Discovery and characterization of a potent activator of the BKCa channel that relives overactive bladder syndrome in rats"],"prefix":"10.1016","volume":"927","author":[{"given":"Heeji","family":"Jo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Jung","family":"Bae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narasaem","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Won","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhan","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Joon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Hee","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chul-Seung","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.ejphar.2022.175055_bib1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0090-4295(02)02243-4","article-title":"The standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society","volume":"61","author":"Abrams","year":"2003","journal-title":"Urology"},{"issue":"3","key":"10.1016\/j.ejphar.2022.175055_bib2","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1152\/physrev.00038.2003","article-title":"Urinary bladder contraction and relaxation: physiology and pathophysiology","volume":"84","author":"Andersson","year":"2004","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.ejphar.2022.175055_bib3","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1113\/jphysiol.1982.sp014370","article-title":"Properties of single calcium-activated potassium channels in cultured rat muscle","volume":"331","author":"Barrett","year":"1982","journal-title":"J. Physiol."},{"issue":"7","key":"10.1016\/j.ejphar.2022.175055_bib4","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1111\/j.1464-410X.2008.07769.x","article-title":"A review of adherence to drug therapy in patients with overactive bladder","volume":"102","author":"Basra","year":"2008","journal-title":"BJU Int."},{"key":"10.1016\/j.ejphar.2022.175055_bib5","doi-asserted-by":"crossref","first-page":"389","DOI":"10.3389\/fphys.2014.00389","article-title":"BK channel activators and their therapeutic perspectives","volume":"5","author":"Bentzen","year":"2014","journal-title":"Front. Physiol."},{"issue":"8","key":"10.1016\/j.ejphar.2022.175055_bib6","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1111\/j.1742-1241.2006.01067.x","article-title":"Solifenacin significantly improves all symptoms of overactive bladder syndrome","volume":"60","author":"Chapple","year":"2006","journal-title":"Int. J. Clin. Pract."},{"issue":"4","key":"10.1016\/j.ejphar.2022.175055_bib7","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1097\/00004647-200104000-00008","article-title":"The maxi-K channel opener BMS-204352 attenuates regional cerebral edema and neurologic motor impairment after experimental brain injury","volume":"21","author":"Cheney","year":"2001","journal-title":"J. Cerebr. Blood Flow Metabol."},{"issue":"4","key":"10.1016\/j.ejphar.2022.175055_bib8","first-page":"R1279","article-title":"Altered regulation of bladder nerve growth factor and neurally mediated hyperactive voiding","volume":"275","author":"Clemow","year":"1998","journal-title":"Am. J. Physiol."},{"issue":"6","key":"10.1016\/j.ejphar.2022.175055_bib9","doi-asserted-by":"crossref","first-page":"442","DOI":"10.4161\/chan.26242","article-title":"A BK (Slo1) channel journey from molecule to physiology","volume":"7","author":"Contreras","year":"2013","journal-title":"Channels"},{"issue":"11","key":"10.1016\/j.ejphar.2022.175055_bib10","doi-asserted-by":"crossref","first-page":"6023","DOI":"10.1073\/pnas.1920008117","article-title":"Loss-of-function BK channel mutation causes impaired mitochondria and progressive cerebellar ataxia","volume":"117","author":"Du","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"issue":"19","key":"10.1016\/j.ejphar.2022.175055_bib11","doi-asserted-by":"crossref","first-page":"11083","DOI":"10.1016\/S0021-9258(19)38560-6","article-title":"Purification and characterization of a unique, potent, peptidyl probe for the high conductance calcium-activated potassium channel from venom of the scorpion Buthus tamulus","volume":"265","author":"Galvez","year":"1990","journal-title":"J. Biol. Chem."},{"issue":"5","key":"10.1016\/j.ejphar.2022.175055_bib12","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1016\/j.ejmech.2008.10.031","article-title":"Design, synthesis and characterization of novel 2-(2,4-disubstituted-thiazole-5-yl)-3-aryl-3H-quinazoline-4-one derivatives as inhibitors of NF-kappaB and AP-1 mediated transcription activation and as potential anti-inflammatory agents","volume":"44","author":"Giri","year":"2009","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejphar.2022.175055_bib13","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1146\/annurev-physiol-022516-034038","article-title":"Regulation of BK channels by beta and gamma subunits","volume":"81","author":"Gonzalez-Perez","year":"2019","journal-title":"Annu. Rev. Physiol."},{"issue":"10","key":"10.1016\/j.ejphar.2022.175055_bib14","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1002\/cbic.200400448","article-title":"Benzofuroindole analogues as potent BK(Ca) channel openers","volume":"6","author":"Gormemis","year":"2005","journal-title":"Chembiochem"},{"issue":"28","key":"10.1016\/j.ejphar.2022.175055_bib15","doi-asserted-by":"crossref","first-page":"11800","DOI":"10.1073\/pnas.0904635106","article-title":"Hypertension of Kcnmb1-\/- is linked to deficient K secretion and aldosteronism","volume":"106","author":"Grimm","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"issue":"3","key":"10.1016\/j.ejphar.2022.175055_bib16","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1124\/mol.105.016170","article-title":"Electrophysiological characterization of benzofuroindole-induced potentiation of large-conductance Ca2+-activated K+ channels","volume":"69","author":"Ha","year":"2006","journal-title":"Mol. Pharmacol."},{"issue":"26","key":"10.1016\/j.ejphar.2022.175055_bib17","doi-asserted-by":"crossref","first-page":"16289","DOI":"10.1074\/jbc.273.26.16289","article-title":"The beta subunit of the high conductance calcium-activated potassium channel. Identification of residues involved in charybdotoxin binding","volume":"273","author":"Hanner","year":"1998","journal-title":"J. Biol. Chem."},{"issue":"7","key":"10.1016\/j.ejphar.2022.175055_bib18","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0068052","article-title":"Neurogenic detrusor overactivity is associated with decreased expression and function of the large conductance voltage- and Ca(2+)-activated K(+) channels","volume":"8","author":"Hristov","year":"2013","journal-title":"PLoS One"},{"issue":"19","key":"10.1016\/j.ejphar.2022.175055_bib19","doi-asserted-by":"crossref","first-page":"5819","DOI":"10.1021\/bi00185a021","article-title":"Tremorgenic indole alkaloids potently inhibit smooth muscle high-conductance calcium-activated potassium channels","volume":"33","author":"Knaus","year":"1994","journal-title":"Biochemistry"},{"issue":"10","key":"10.1016\/j.ejphar.2022.175055_bib21","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1111\/bph.13085","article-title":"Effects of the novel BK (KCa 1.1) channel opener GoSlo-SR-5-130 are dependent on the presence of BKbeta subunits","volume":"172","author":"Large","year":"2015","journal-title":"Br. J. Pharmacol."},{"issue":"2","key":"10.1016\/j.ejphar.2022.175055_bib22","doi-asserted-by":"crossref","first-page":"R378","DOI":"10.1152\/ajpregu.00458.2009","article-title":"BK channel activation by NS11021 decreases excitability and contractility of urinary bladder smooth muscle","volume":"298","author":"Layne","year":"2010","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"issue":"1","key":"10.1016\/j.ejphar.2022.175055_bib23","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.jbiotec.2013.06.007","article-title":"Development of cell-based assay system that utilizes a hyperactive channel mutant for high-throughput screening of BK(Ca) channel modulators","volume":"167","author":"Lee","year":"2013","journal-title":"J. Biotechnol."},{"issue":"2","key":"10.1016\/j.ejphar.2022.175055_bib24","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1124\/mol.115.102939","article-title":"Urinary bladder-relaxant effect of kurarinone depending on potentiation of large-conductance Ca2+-activated K+ channels","volume":"90","author":"Lee","year":"2016","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.ejphar.2022.175055_bib25","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/bs.irn.2016.03.015","article-title":"Modulation of BK channel function by auxiliary beta and gamma subunits","volume":"128","author":"Li","year":"2016","journal-title":"Int. Rev. Neurobiol."},{"issue":"26","key":"10.1016\/j.ejphar.2022.175055_bib26","doi-asserted-by":"crossref","first-page":"3835","DOI":"10.2174\/1381612821666150407101614","article-title":"Efficacy of andolast in mild to moderate asthma: a randomized, controlled, double-blind multicenter study (the andast trial)","volume":"21","author":"Malerba","year":"2015","journal-title":"Curr. Pharmaceut. Des."},{"key":"10.1016\/j.ejphar.2022.175055_bib27","doi-asserted-by":"crossref","first-page":"F257","DOI":"10.1152\/ajprenal.00048.2020","article-title":"Urinary bladder smooth muscle ion channels: expression, function, and regulation in health and disease","volume":"319","author":"Malysz","year":"2020","journal-title":"Am. J. Physiol. Ren. Physiol."},{"issue":"10","key":"10.1016\/j.ejphar.2022.175055_bib28","doi-asserted-by":"crossref","first-page":"5562","DOI":"10.1073\/pnas.100118597","article-title":"A neuronal beta subunit (KCNMB4) makes the large conductance, voltage- and Ca2+-activated K+ channel resistant to charybdotoxin and iberiotoxin","volume":"97","author":"Meera","year":"2000","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"issue":"35","key":"10.1016\/j.ejphar.2022.175055_bib29","doi-asserted-by":"crossref","first-page":"36746","DOI":"10.1074\/jbc.M405621200","article-title":"Overactive bladder and incontinence in the absence of the BK large conductance Ca2+-activated K+ channel","volume":"279","author":"Meredith","year":"2004","journal-title":"J. Biol. Chem."},{"issue":"3","key":"10.1016\/j.ejphar.2022.175055_bib30","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1080\/13697137.2018.1543263","article-title":"The prevalence of urinary incontinence","volume":"22","author":"Milsom","year":"2019","journal-title":"Climacteric"},{"key":"10.1016\/j.ejphar.2022.175055_bib31","doi-asserted-by":"crossref","unstructured":"National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals, 2011. Guide for the Care and Use of Laboratory Animals, eighth ed. National Academies Press, Washington (DC). https:\/\/doi:10.17226\/12910.","DOI":"10.17226\/12910"},{"issue":"4","key":"10.1016\/j.ejphar.2022.175055_bib32","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1111\/j.1464-410X.2010.09935.x","article-title":"Effects of potassium channel modulators on myogenic spontaneous phasic contractile activity in human detrusor from neurogenic patients","volume":"108","author":"Oger","year":"2011","journal-title":"BJU Int."},{"issue":"4","key":"10.1016\/j.ejphar.2022.175055_bib33","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1085\/jgp.200409236","article-title":"Differential effects of beta 1 and beta 2 subunits on BK channel activity","volume":"125","author":"Orio","year":"2005","journal-title":"J. Gen. Physiol."},{"issue":"5832","key":"10.1016\/j.ejphar.2022.175055_bib34","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/293471a0","article-title":"Single channel recordings of Ca2+-activated K+ currents in rat muscle cell culture","volume":"293","author":"Pallotta","year":"1981","journal-title":"Nature"},{"key":"10.1016\/j.ejphar.2022.175055_bib35","article-title":"Synthesis, biological evaluation and molecular docking studies of novel quinazolinones as antitubercular and antimicrobial agents","volume":"108","author":"Pandey","year":"2021","journal-title":"Bioorg. Chem."},{"issue":"5","key":"10.1016\/j.ejphar.2022.175055_bib47","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.ceca.2003.10.006","article-title":"Some precautions in using chelators to buffer metals in biological solutions","volume":"35","author":"Patton","year":"2004","journal-title":"Cell Calcium"},{"issue":"4","key":"10.1016\/j.ejphar.2022.175055_bib36","first-page":"R1366","article-title":"Spinal and peripheral mechanisms contributing to hyperactive voiding in spontaneously hypertensive rats","volume":"275","author":"Persson","year":"1998","journal-title":"Am. J. Physiol."},{"issue":"6","key":"10.1016\/j.ejphar.2022.175055_bib37","doi-asserted-by":"crossref","first-page":"R571","DOI":"10.1152\/ajpregu.00142.2014","article-title":"Central role of the BK channel in urinary bladder smooth muscle physiology and pathophysiology","volume":"307","author":"Petkov","year":"2014","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"issue":"4","key":"10.1016\/j.ejphar.2022.175055_bib38","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1124\/mol.111.075853","article-title":"Selective, direct activation of high-conductance, calcium-activated potassium channels causes smooth muscle relaxation","volume":"81","author":"Ponte","year":"2012","journal-title":"Mol. Pharmacol."},{"issue":"10","key":"10.1016\/j.ejphar.2022.175055_bib39","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1002\/cmdc.201200321","article-title":"Structure-activity relationships of a novel group of large-conductance Ca(2+)-activated K(+) (BK) channel modulators: the GoSlo-SR family","volume":"7","author":"Roy","year":"2012","journal-title":"ChemMedChem"},{"key":"10.1016\/j.ejphar.2022.175055_bib41","doi-asserted-by":"crossref","first-page":"383","DOI":"10.3389\/fphys.2014.00383","article-title":"Pharmacological consequences of the coexpression of BK channel alpha and auxiliary beta subunits","volume":"5","author":"Torres","year":"2014","journal-title":"Front. Physiol."},{"issue":"5","key":"10.1016\/j.ejphar.2022.175055_bib42","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1177\/1756287215591763","article-title":"Clinical use of the beta3 adrenoceptor agonist mirabegron in patients with overactive bladder syndrome","volume":"7","author":"Vij","year":"2015","journal-title":"Ther. Adv. Urol."},{"key":"10.1016\/j.ejphar.2022.175055_bib43","doi-asserted-by":"crossref","DOI":"10.1155\/2013\/387191","article-title":"Synthesis, antimicrobial, and anti-HIV1 activity of quinazoline-4(3H)-one derivatives","author":"Vijayakumar","year":"2013","journal-title":"J. Appl. Chem."},{"issue":"4","key":"10.1016\/j.ejphar.2022.175055_bib44","doi-asserted-by":"crossref","first-page":"336","DOI":"10.4274\/balkanmedj.2017.0986","article-title":"Expanding the phenotype of homozygous KCNMA1 mutations; dyskinesia, epilepsy, intellectual disability, cerebellar and corticospinal tract atrophy","volume":"35","author":"Yesil","year":"2018","journal-title":"Balkan Med. J."},{"issue":"35","key":"10.1016\/j.ejphar.2022.175055_bib45","doi-asserted-by":"crossref","first-page":"30882","DOI":"10.1074\/jbc.M505302200","article-title":"Activation of the BK (SLO1) potassium channel by mallotoxin","volume":"280","author":"Zakharov","year":"2005","journal-title":"J. Biol. Chem."}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299922003168?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299922003168?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T04:18:25Z","timestamp":1762143505000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299922003168"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7]]},"references-count":44,"alternative-id":["S0014299922003168"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2022.175055","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2022,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Discovery and characterization of a potent activator of the BKCa channel that relives overactive bladder syndrome in rats","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2022.175055","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"175055"}}