CGMP and mitochondrial K+ channels—Compartmentalized but closely connected in cardioprotection. (9th July 2021)

• Record Type: Journal Article
• Authors: Lukowski, Robert; Cruz Santos, Melanie; Kuret, Anna; Ruth, Peter
• Other Names: Lukowski Robert guestEditor.; Feil Robert guestEditor.
• Is Part Of: British journal of pharmacology. Volume 179:Number 11(2022)
• Page Start: 2344
• Page End: 2360
• Publication Date: 2021-07-09
• Subjects: 3', 5'‐cyclic guanosine monophosphate (cGMP) -- atrial natriuretic peptide (ANP) -- brain (or B‐type) natriuretic peptide (BNP) -- cGMP‐dependent protein kinase I (cGKI) -- C‐type natriuretic peptide (CNP) -- mitochondrial ATP‐sensitive potassium (K+) channel (mitoKATP) -- mitochondrial calcium (Ca2+)‐activated K+ channels of the BK type (mitoBK) -- neutral endopeptidase (NEP) -- nitric oxide (NO) -- NO synthase (NOS) -- NO‐sensitive (soluble) guanylyl cyclase (GC or NO‐GC) -- phosphodiesterase (PDE); Pharmacology -- Periodicals; Chemotherapy -- Periodicals; Drug Therapy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/bph.15536
• Languages: English
• ISSNs: 0007-1188

Abstract

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 KATP ) and Ca 2+ ‐activated potassium channels of the BK type ( mito BK). Accordingly, agents activating mito KATP 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 KATP 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