title: Alternative paradigms for ion channelopathies: disorders of ion channel membrane trafficking and posttranslational modification.
abstract: Channelopathies are a diverse set of disorders associated with defects in ion channel (and transporter) function. Although the vast majority of channelopathies are linked with inherited mutations that alter ion channel biophysical properties, another group of similar disorders has emerged that alter ion channel synthesis, membrane trafficking, and/or posttranslational modifications. In fact, some electrical and episodic disorders have now been identified that are not defects in the ion channel but instead reflect dysfunction in an ion channel (or transporter) regulatory protein. This review focuses on alternative paradigms for physiological disorders associated with protein biosynthesis, folding, trafficking, and membrane retention. Furthermore, the review highlights the role of aberrant posttranslational modifications in acquired channelopathies.
authors.affiliation: The Dorothy M. Davis Heart & Lung Research Institute.
authors.forename: Jerry
authors.initials: J
authors.lastname: Curran
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Mohler
mesh_terms: D002462:Cell Membrane / Q000235:genetics / Q000502:physiology*; D053447:Channelopathies / Q000235:genetics / Q000503:physiopathology*; D003599:Cytoskeleton / Q000235:genetics / Q000502:physiology; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D017510:Protein Folding; D011499:Protein Processing, Post-Translational / Q000235:genetics / Q000502:physiology*; D021381:Protein Transport / Q000235:genetics / Q000502:physiology*
chemical_list: D007473:Ion Channels
keywords: arrhythmia; cytoskeleton; heart failure; phosphorylation; protein trafficking; targeting