title: Ion channel phosphorylopathy: a link between genomic variation and human disease.
abstract: Voltage-gated ion channels (VGIC) regulate many important physiological events, including muscle contraction, brain function, and secretion. Mutations that inhibit or up-regulate VGIC activities can dramatically interfere with the normal function of several organs, leading to unpredictable failure and therefore poor quality of life or even death. Many genomic variations that change amino acids in cytoplasmic domains of ion channels have been found to be associated with several diseases, including cardiac arrhythmias and neurodegeneration. However, a mechanism linking these mutations to ion channel malfunction has not been clearly established and in some cases is totally unknown. This concept article gives an overview on a possible mechanism by which disease-associated mutations in cytoplasmic domains of ion channels can affect channel activity by creating or disrupting phosphorylation sites for specific kinases. We call these events "ion channel phosphorylopathies". Understanding ion channel phosphorylopathies offers the opportunity to find a mechanism linking genomic variations to human disease and is crucial to the process of designing an effective pharmacological strategy.
authors.affiliation: Department of Molecular Pharmacology and Therapeutics, Loyola University Medical Center, 2160 South First Ave., Bldg. 102, Rm. 3621, Maywood, IL 60153, USA. sagentile@lumc.edu
authors.forename: Saverio
authors.initials: S
authors.lastname: Gentile
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases; D000595:Amino Acid Sequence; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000737:chemistry / Q000378:metabolism; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D014644:Genetic Variation; D006801:Humans; D007473:Ion Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D026902:Potassium Channel Blockers / Q000737:chemistry; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D020746:Calcium Channels, L-Type; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D007473:Ion Channels; C419385:L-type calcium channel alpha(1C); D026902:Potassium Channel Blockers; D064413:3-Phosphoinositide-Dependent Protein Kinases; D017346:Protein Serine-Threonine Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2