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Remarkably, targets and mechanisms underlying this action remain largely unidentified. Artery diameter is regulated by myocyte Ca<jats:sup>2+<\/jats:sup>sparks, a vasodilatory signal contributed to by type 2 ryanodine receptors (RyR2). Using laser confocal microscopy in rat cerebral arteries and bilayer electrophysiology we unveil that ethanol inhibits both Ca<jats:sup>2+<\/jats:sup>spark and RyR2 activity with IC<jats:sub>50<\/jats:sub><jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/feb2s0014579314001987-math-si2.gif\" xlink:title=\"urn:x-wiley:00145793:media:feb2s0014579314001987:feb2s0014579314001987-math-si2\"\/>20 mM, placing RyR2 among the ion channels that are most sensitive to ethanol. Alcohol directly targets RyR2 and its lipid microenvironment, leading to stabilization of RyR2 closed states.<\/jats:p>","DOI":"10.1016\/j.febslet.2014.03.005","type":"journal-article","created":{"date-parts":[[2014,3,16]],"date-time":"2014-03-16T01:15:46Z","timestamp":1394932546000},"page":"1659-1665","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Type 2 ryanodine receptors are highly sensitive to alcohol"],"prefix":"10.1002","volume":"588","author":[{"given":"Yanping","family":"Ye","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuihuan","family":"Jian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan H.","family":"Jaggar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna N.","family":"Bukiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex M.","family":"Dopico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,3,12]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"21","article-title":"Alcohol and the cardiovascular system: molecular mechanisms for beneficial and harmful action","volume":"21","author":"Zakhari S.","year":"1997","journal-title":"Alcohol Health Res. 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