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These beneficial effects were attributed to NO\u2010sensitive GC induced cGMP production leading to activation of cGMP\u2010dependent protein kinase I (cGKI). cGKI in turn phosphorylates many substrates, which eventually facilitate opening of mitochondrial ATP\u2010sensitive potassium channels (<jats:italic>mito<\/jats:italic>K<jats:sub>ATP<\/jats:sub>) and Ca<jats:sup>2+<\/jats:sup>\u2010activated potassium channels of the BK type (<jats:italic>mito<\/jats:italic>BK). Accordingly, agents activating <jats:italic>mito<\/jats:italic>K<jats:sub>ATP<\/jats:sub> or <jats:italic>mito<\/jats:italic>BK provide protection against I\/R\u2010induced damages. Here, we provide an up\u2010to\u2010date summary of the infarct\u2010limiting actions exhibited by the GC\/cGMP axis and discuss how <jats:italic>mito<\/jats:italic>K<jats:sub>ATP<\/jats:sub> and <jats:italic>mito<\/jats:italic>BK, which are present at the inner mitochondrial membrane, confer mito\u2010 and cytoprotective effects on cardiomyocytes exposed to I\/R injury. In view of this, we believe that the functional connection between the cGMP cascade and <jats:italic>mito<\/jats:italic>K<jats:sup>+<\/jats:sup> channels should be exploited further as adjunct to reperfusion therapy in myocardial infarction.<\/jats:p><\/jats:sec><jats:sec><jats:title>LINKED ARTICLES<\/jats:title><jats:p>This article is part of a themed issue on cGMP Signalling in Cell Growth and Survival. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v179.11\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v179.11\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15536","type":"journal-article","created":{"date-parts":[[2021,5,15]],"date-time":"2021-05-15T18:23:30Z","timestamp":1621103010000},"page":"2344-2360","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["cGMP and mitochondrial K<sup>+<\/sup> channels\u2014Compartmentalized but closely connected in cardioprotection"],"prefix":"10.1111","volume":"179","author":[{"given":"Robert","family":"Lukowski","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Toxicology and Clinical Pharmacy, Institute of Pharmacy University of Tuebingen  Tuebingen 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