cGMP and mitochondrial K⁺ channels—Compartmentalized but closely connected in cardioprotection

The 3′,5′‐cGMP pathway triggers cytoprotective responses and improves cardiomyocyte survival during myocardial ischaemia and reperfusion (I/R) injury. These beneficial effects were attributed to NO‐sensitive GC induced cGMP production leading to activation of cGMP‐dependent protein kinase I (cGKI). cGKI in turn phosphorylates many substrates, which eventually facilitate opening of mitochondrial ATP‐sensitive potassium channels ( mito K ATP ) and Ca 2+ ‐activated potassium channels of the BK type ( mito BK). Accordingly, agents activating mito K ATP or mito BK provide protection against I/R‐induced damages. Here, we provide an up‐to‐date summary of the infarct‐limiting actions exhibited by the GC/cGMP axis and discuss how mito K ATP and mito BK, which are present at the inner mitochondrial membrane, confer mito‐ 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 mito K + channels should be exploited further as adjunct to reperfusion therapy in myocardial infarction. LINKED ARTICLES 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 http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.11/issuetoc