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

Abstract

ATP-sensitive potassium channels (K_ATP 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 K_ATP channel repolarizes the membrane potential and decreases early afterdepolarization (EAD)-mediated arrhythmias. K_ATP 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 K_ATP channel, which induces the repolarization of the membrane and decreases the occurrence of malignant arrhythmia. Accumulated evidence indicates that mutation of K_ATP channels deteriorates the regulatory roles in mutation-related diseases. However, patients with mutations in K_ATP channels still have no efficient treatment. Hence, in this study, we describe the role of K_ATP channels and subunits in angiocardiopathy, summarize the mutations of the K_ATP channels and the functional regulation of small active molecules in K_ATP channels, elucidate the potential mechanisms of mutant K_ATP channels and provide insight into clinical therapeutic strategies.

Keywords: KATP channels; channelopathy; mitoKATP channels; mutation; myocardial ischemia; small active molecules.