Small-conductance Ca2+-activated K+ channels: insights into their roles in cardiovascular disease

Life-threatening malignant arrhythmias in pathophysiological conditions can increase the mortality and morbidity of patients with cardiovascular diseases. Cardiac electrical activity depends on the coordinated propagation of excitatory stimuli and the generation of action potentials in cardiomyocytes. Action potential formation results from the opening and closing of ion channels. Recent studies have indicated that small-conductance calcium-activated potassium (SK) channels play a critical role in cardiac repolarization in pathophysiological but not normal physiological conditions. The aim of this review is to describe the role of SK channels in healthy and diseased hearts, to suggest cardiovascular pathophysiologic targets for intervention, and to discuss studies of agents that target SK channels for the treatment of cardiovascular diseases. Drugs that target ion channels involved in controlling heartbeats could help correct irregular cardiac rhythms. Dai-Min Zhang from Nanjing First Hospital, Nanjing Medical University, China, and colleagues reviewed the function of small-conductance calcium-activated potassium (SK) channels in the heart under normal and disease conditions. These pore-forming proteins, which are opened by calcium and allow potassium to cross the cell membrane, help re-establish a normal electrical balance at the end of each heartbeat. When the channels become overactive and misfire, they can cause arrhythmias and heart failure. The authors discuss how drugs that inhibit SK channels hold promise for treating diseases associated with cardiac arrhythmias, such as atrial fibrillation. Blockade of SK channels can, however, induce arrhythmias in certain clinical situations, so further research is needed to determine when this therapeutic strategy would be safe and appropriate.