{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T08:22:17Z","timestamp":1774686137361,"version":"3.50.1"},"reference-count":61,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,1,26]],"date-time":"2020-01-26T00:00:00Z","timestamp":1579996800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["201408080102"],"award-info":[{"award-number":["201408080102"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>BK channels play important roles in various physiological and pathophysiological processes and thus have been the target of several drug development programmes focused on creating new efficacious BK channel openers, such as the GoSlo\u2010SR compounds. However, the effect of GoSlo\u2010SR compounds on vascular smooth muscle has not been studied. Therefore, we tested the hypothesis that GoSlo\u2010SR compounds dilate arteries exclusively by activating BK channels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Experiments were performed on rat <jats:italic>Gracilis<\/jats:italic> muscle, saphenous, mesenteric and tail arteries using isobaric and isometric myography, sharp microelectrodes, digital droplet PCR and the patch\u2010clamp technique.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>GoSlo\u2010SR compounds dilated isobaric and relaxed and hyperpolarised isometric vessel preparations and their effects were abolished after (a) functionally eliminating K<jats:sup>+<\/jats:sup> channels by pre\u2010constriction with 50 mM KCl or (b) blocking all K<jats:sup>+<\/jats:sup> channels known to be expressed in vascular smooth muscle. However, these effects were not blocked when BK channels were inhibited. Surprisingly, the K<jats:sub>v<\/jats:sub>7 channel inhibitor XE991 reduced their effects considerably, but neither K<jats:sub>v<\/jats:sub>1 nor K<jats:sub>v<\/jats:sub>2 channel blockers altered the inhibitory effects of GoSlo\u2010SR. However, the combined blockade of BK and K<jats:sub>v<\/jats:sub>7 channels abolished the GoSlo\u2010SR\u2010induced relaxation. GoSlo\u2010SR compounds also activated K<jats:sub>v<\/jats:sub>7.4 and K<jats:sub>v<\/jats:sub>7.5 channels expressed in HEK 293 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>This study shows that GoSlo\u2010SR compounds are effective relaxants in vascular smooth muscle and mediate their effects by a combined activation of BK and K<jats:sub>v<\/jats:sub>7.4\/K<jats:sub>v<\/jats:sub>7.5 channels. Activation of K<jats:sub>v<\/jats:sub>1, K<jats:sub>v<\/jats:sub>2 or K<jats:sub>v<\/jats:sub>7.1 channels or other vasodilator pathways seems not to be involved.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14910","type":"journal-article","created":{"date-parts":[[2019,10,28]],"date-time":"2019-10-28T18:54:33Z","timestamp":1572288873000},"page":"1164-1186","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Vasodilation of rat skeletal muscle arteries by the novel BK channel opener GoSlo is mediated by the simultaneous activation of BK and K<sub>v<\/sub>7 channels"],"prefix":"10.1111","volume":"177","author":[{"given":"Olga","family":"Zavaritskaya","sequence":"first","affiliation":[{"name":"Centre for Biomedicine and Medical Technology Mannheim (CBTM), Research Division Cardiovascular Physiology, Medical Faculty Mannheim Heidelberg University  Mannheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Srikanth","family":"Dudem","sequence":"additional","affiliation":[{"name":"Smooth Muscle Research Centre Dundalk Institute of Technology  Dundalk Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongyu","family":"Ma","sequence":"additional","affiliation":[{"name":"Centre for Biomedicine and Medical Technology Mannheim (CBTM), Research Division Cardiovascular Physiology, Medical Faculty Mannheim Heidelberg University  Mannheim Germany"},{"name":"Department of Cardiology The First Affiliated Hospital of Anhui Medical University  Anhui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaneez E.","family":"Rabab","sequence":"additional","affiliation":[{"name":"Smooth Muscle Research Centre Dundalk Institute of Technology  Dundalk Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Albrecht","sequence":"additional","affiliation":[{"name":"Centre for Biomedicine and Medical Technology Mannheim (CBTM), Research Division Cardiovascular Physiology, Medical Faculty Mannheim Heidelberg University  Mannheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dmitry","family":"Tsvetkov","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center (ECRC), a joint cooperation between the Charit\u00e9 Medical Faculty and the Max Delbr\u00fcck Center for Molecular Medicine (MDC)  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Kassmann","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center (ECRC), a joint cooperation between the Charit\u00e9 Medical Faculty and the Max Delbr\u00fcck Center for Molecular Medicine (MDC)  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith","family":"Thornbury","sequence":"additional","affiliation":[{"name":"Smooth Muscle Research Centre Dundalk Institute of Technology  Dundalk Ireland"},{"name":"Ion Channel Biotechnology Centre Dundalk Institute of Technology  Dundalk Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitko","family":"Mladenov","sequence":"additional","affiliation":[{"name":"Centre for Biomedicine and Medical Technology Mannheim (CBTM), Research Division Cardiovascular Physiology, Medical Faculty Mannheim Heidelberg University  Mannheim Germany"},{"name":"Institute of Biology, Faculty of Natural Sciences and Mathematics, Sts. 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