Functional Regulation of K(ATP) Channels and Mutant Insight Into Clinical Therapeutic Strategies in Cardiovascular Diseases

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.