title: Pathomechanisms in channelopathies of skeletal muscle and brain.
abstract: Ion channelopathies are a diverse array of human disorders caused by mutations in ion channel genes. This review focuses on the pathogenic mechanisms of channelopathies affecting skeletal muscle and brain arising from mutations of voltage-gated ion channels and fast ligand-gated ion channels expressed at the surface membrane. Derangements in channel function alter the electrical excitability of the cell and thereby increase susceptibility to transient symptomatic attacks including myasthenia, periodic paralysis, myotonic stiffness, seizures, headache, dyskinesia, or episodic ataxia. Although these disorders are rare, they stand out as exemplary cases for which disease pathogenesis can be traced from a point mutation to altered protein function, to altered cellular activity, and to clinical phenotype. The study of these disorders has provided insights on channel structure-function relations, the physiological roles of ion channels, and rational approaches toward therapeutic intervention for many disorders of cellular excitability.
authors.affiliation: Department of Neurology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. steve.cannon@utsouthwestern.edu
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Cannon
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology*; D001927:Brain Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D008958:Models, Molecular; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology*; D009135:Muscular Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D009154:Mutation
chemical_list: D007473:Ion Channels