Ion channels as part of macromolecular multiprotein complexes: Clinical significance

Ion channels and Ca2+-handling proteins involved in the regulation of cardiac electrophysiology and contractility are organized in macromolecular multiprotein complexes. Recent molecular and cellular studies have significantly enhanced our understanding of the composition of these macromolecular complexes and have helped to elucidate their role in the dynamic regulation of ion channel function. Moreover, it has become clear that alterations in the composition of ion channel macromolecular complexes, for example, due to genetic mutations or acquired alterations in the expression of individual components, may lead to ion channel dysfunction and arrhythmogenesis. Here, we review novel insights into the composition of the major ion channel macromolecular complexes and discuss the potential clinical significance of alterations in these dynamic multiprotein structures.