Coordinating electrical activity of the heart: ankyrin polypeptides in human cardiac disease

Introduction: Over the past ten years, ankyrin polypeptides have emerged as players in cardiac excitation?contraction coupling. Once thought to solely play a structural role, loss-of-function variants of genes encoding ankyrin polypeptides have highlighted how this protein mediates subcellular localization of various electrical components of the excitation?contraction coupling machinery. Evidence has revealed how disruption of this localization is the primary cause of various cardiomyopathies, ranging from long-QT syndrome 4, to sinus node disease, to more common forms of arrhythmias. Areas covered: The roles of ankyrin polypeptides in excitation?contraction coupling in the heart and the development of ankyrin-specific cardiomyopathies. How ankyrin polypeptides may be involved in structural and electrical remodeling of the heart, post-myocardial infarct. How ankyrin interactions with membrane-bound ion channels may regulate these channels' response to stimuli. New data, which offers the potential for unique therapies, for not only combating heart disease, but also for wider applications to various disease states. Expert opinion: The ankyrin family of adapter proteins is emerging as an intimate player in cardiac excitation?contraction coupling. Until recently, these proteins have gone largely unappreciated for their importance in proper cardiac function. New insights into how these proteins function within the heart are offering potentially new avenues for therapies against cardiomyopathy.