{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T10:42:28Z","timestamp":1785494548990,"version":"3.56.0"},"reference-count":38,"publisher":"American Physiological Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2013,6,1]]},"abstract":"<jats:p> The voltage-sensitive dye bis-(1,3-dibutylbarbituric acid)trimethine oxonol [DiBAC<jats:sub>4<\/jats:sub>(3)] has been reported as a novel large-conductance Ca<jats:sup>2+<\/jats:sup>-activated K<jats:sup>+<\/jats:sup> (BK) channel activator with selectivity for its \u03b2<jats:sub>1<\/jats:sub>- or \u03b2<jats:sub>4<\/jats:sub>-subunits. In arterial smooth muscle, BK channels are formed by a pore-forming \u03b1-subunit and a smooth muscle-abundant regulatory \u03b2<jats:sub>1<\/jats:sub>-subunit. This tissue specificity has driven extensive pharmacological research aimed at regulating arterial tone. Using animals with a disruption of the gene for the \u03b2<jats:sub>1<\/jats:sub>-subunit, we explored the effects of DiBAC<jats:sub>4<\/jats:sub>(3) in native channels from arterial smooth muscle. We tested the hypothesis that, in native BK channels, activation by DiBAC<jats:sub>4<\/jats:sub>(3) relies mostly on its \u03b1-subunit. We studied BK channels from wild-type and transgenic \u03b2<jats:sub>1<\/jats:sub>-knockout mice in excised patches. BK channels from brain arteries, with or without the \u03b2<jats:sub>1<\/jats:sub>-subunit, were similarly activated by DiBAC<jats:sub>4<\/jats:sub>(3). In addition, we found that saturating concentrations of DiBAC<jats:sub>4<\/jats:sub>(3) (\u223c30 \u03bcM) promote an unprecedented persistent activation of the channel that negatively shifts its voltage dependence by as much as \u2212300 mV. This \u201csweet spot\u201d for persistent activation is independent of Ca<jats:sup>2+<\/jats:sup> and\/or the \u03b2<jats:sub>1\u20134<\/jats:sub>-subunits and is fully achieved when DiBAC<jats:sub>4<\/jats:sub>(3) is applied to the intracellular side of the channel. Arterial BK channel response to DiBAC<jats:sub>4<\/jats:sub>(3) varies across species and\/or vascular beds. DiBAC<jats:sub>4<\/jats:sub>(3) unique effects can reveal details of BK channel gating mechanisms and help in the rational design of BK channel activators. <\/jats:p>","DOI":"10.1152\/ajpheart.00939.2012","type":"journal-article","created":{"date-parts":[[2013,3,29]],"date-time":"2013-03-29T21:31:16Z","timestamp":1364592676000},"page":"H1471-H1482","source":"Crossref","is-referenced-by-count":12,"title":["DiBAC<sub>4<\/sub>(3) hits a \u201csweet spot\u201d for the activation of arterial large-conductance Ca<sup>2+<\/sup>-activated potassium channels independently of the \u03b2<sub>1<\/sub>-subunit"],"prefix":"10.1152","volume":"304","author":[{"given":"Fabiana S.","family":"Scornik","sequence":"first","affiliation":[{"name":"Cardiovascular Genetics Center, Institut de Investigaci\u00f3 Biom\u00e8dica de Girona, and  Department of Medical Sciences, School of Medicine, University of Girona, Girona, Spain; and"},{"name":"Masonic Medical Research Laboratory, Utica, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald S.","family":"Bucciero","sequence":"additional","affiliation":[{"name":"Masonic Medical Research Laboratory, Utica, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuesheng","family":"Wu","sequence":"additional","affiliation":[{"name":"Masonic Medical Research Laboratory, Utica, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabet","family":"Selga","sequence":"additional","affiliation":[{"name":"Cardiovascular Genetics Center, Institut de Investigaci\u00f3 Biom\u00e8dica de Girona, and  Department of Medical Sciences, School of Medicine, University of Girona, Girona, Spain; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Bosch Calero","sequence":"additional","affiliation":[{"name":"Cardiovascular Genetics Center, Institut de Investigaci\u00f3 Biom\u00e8dica de Girona, and  Department of Medical Sciences, School of 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