Functional Regulation of KATP Channels and Mutant Insight Into Clinical Therapeutic Strategies in Cardiovascular Diseases

Abstract

ATP-sensitive potassium channels (KATP channels) play pivotal roles in excitable cells and link cellular metabolism with membrane excitability. The action potential converts electricity into dynamics by ion channel-mediated ion exchange to generate systole, involved in every heartbeat. Activation of the KATP channel repolarizes the membrane potential and decreases early afterdepolarization (EAD)-mediated arrhythmias. KATP channels in cardiomyocytes have less function under physiological conditions but they open during severe and prolonged anoxia due to a reduced ATP/ADP ratio, lessening cellular excitability and thus preventing action potential generation and cell contraction. Small active molecules activate and enhance the opening of the KATP channel, which induces the repolarization of the membrane and decreases the occurrence of malignant arrhythmia. Accumulated evidence indicates that mutation of KATP channels deteriorates the regulatory roles in mutation-related diseases. However, patients with mutations in KATP channels still have no efficient treatment. Hence, in this study, we describe the role of KATP channels and subunits in angiocardiopathy, summarize the mutations of the KATP channels and the functional regulation of small active molecules in KATP channels, elucidate the potential mechanisms of mutant KATP channels and provide insight into clinical therapeutic strategies.

Motor Dysfunction of Gastric Antral Smooth Muscle in Diabetic Rats: Contribution of ATP-Dependent Potassium Channels

“…SUR subunits are also sensitive to the K ATP channel openers diazoxide and pinacidil and the blocker glibenclamide. [ 27 ] Our molecular assay detected the expression of Kir6.1 and SUR2B subunit proteins of K ATP channels in the rat antral muscle. This subunit profile has been suggested for the K ATP channel in gastric smooth muscle cells of guinea pig.…”

miRNA Expression Profiles in Isolated Ventricular Cardiomyocytes: Insights into Doxorubicin-Induced Cardiotoxicity

“…Thus, we evaluated the gene expression levels of several genes in cardiomyocytes exposed to 10 µM DOX for 1 h and 22 h by RT-qPCR. KATP channels comprise three functional subunits: SUR2A, Kir6.1, and Kir6.2, which the ABCC9, KCNJ8, and KCNJ11 genes encode, respectively [28]. To determine whether DOX alters the expression of KATP-encoding genes, we evaluated mRNA levels in cardiomyocytes exposed or not to 10 µM of DOX at the previously defined time points.…”