cGMP and mitochondrial K<sup>+</sup> channels—Compartmentalized but closely connected in cardioprotection
Robert Łukowski, Melanie Cruz Santos, Anna Kuret, Peter Ruth
Abstract
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