{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T12:08:24Z","timestamp":1791029304743,"version":"4.1.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2000,2]]},"abstract":"<jats:p><jats:italic>Background<\/jats:italic>\u2014Nitric oxide (NO) has been implicated as a mediator of \u201csecond-window\u201d ischemic preconditioning, and mitochondrial ATP-dependent K<jats:sup>+<\/jats:sup>(mitoK<jats:sub>ATP<\/jats:sub>) channels are the likely effectors. The links between NO and mitoK<jats:sub>ATP<\/jats:sub>channels are unknown.<\/jats:p><jats:p><jats:italic>Methods and Results<\/jats:italic>\u2014We measured mitochondrial redox potential as an index of mitoK<jats:sub>ATP<\/jats:sub>channel opening in rabbit ventricular myocytes. The NO donor<jats:italic>S<\/jats:italic>-nitroso-<jats:italic>N<\/jats:italic>-acetyl-<jats:sc>dl<\/jats:sc>-penicillamine (SNAP, 0.1 to 1 mmol\/L) oxidized the mitochondrial matrix dose-dependently without activating sarcolemmal K<jats:sub>ATP<\/jats:sub>channels. SNAP-induced oxidation was blocked by the selective mitoK<jats:sub>ATP<\/jats:sub>channel blocker 5-hydroxydecanoate and by the NO scavenger 2-(4-carboxyphenyl)-4,4\u2032,5,5\u2032-tetramethylimidazole-1-oxyl-3-oxide. SNAP-induced mitochondrial oxidation was detectable either by photomultiplier tube recordings of flavoprotein fluorescence or by confocal imaging. SNAP also enhanced the oxidative effects of diazoxide when both agents were applied together. Exposure to 1 mmol\/L 8Br-cGMP failed to mimic the effects of SNAP.<\/jats:p><jats:p><jats:italic>Conclusions<\/jats:italic>\u2014NO directly activates mitoK<jats:sub>ATP<\/jats:sub>channels and potentiates the ability of diazoxide to open these channels. These results provide novel mechanistic links between NO-induced cardioprotection and mitoK<jats:sub>ATP<\/jats:sub>channels.<\/jats:p>","DOI":"10.1161\/01.cir.101.4.439","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:42:29Z","timestamp":1339461749000},"page":"439-445","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":269,"title":["Activation of Mitochondrial ATP-Dependent Potassium Channels by Nitric Oxide"],"prefix":"10.1161","volume":"101","author":[{"given":"Norihito","family":"Sasaki","sequence":"first","affiliation":[{"name":"From the Institute of Molecular Cardiobiology, Johns Hopkins University, Baltimore, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Sato","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Cardiobiology, Johns Hopkins University, Baltimore, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Ohler","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Cardiobiology, Johns Hopkins University, Baltimore, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"O\u2019Rourke","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Cardiobiology, Johns Hopkins University, Baltimore, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Marba\u0301n","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Cardiobiology, Johns Hopkins University, Baltimore, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.1.304"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.18.11038"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3320673"},{"key":"e_1_3_2_4_2","first-page":"H1650","volume":"263","year":"1992","unstructured":"Nakanishi K, Vinten-Johansen J, Lefer DJ, Zhao Z, Fowler WC III, McGee S, Johnston WE. 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