Voltage-gated ion channelopathies: inherited disorders caused by abnormal sodium, chloride, and calcium regulation in skeletal muscle.
The pathological genetic defects in the inherited myotonias and periodic paralyses were recently elucidated using molecular genetic studies. These disorders are usually transmitted as a dominant trait from an affected parent to a child. The many clinical symptoms include cold-induced uncontrollable contraction of muscle, potassium-induced contraction and paralysis, myotonia with dramatic muscular hypertrophy, muscle stiffness, and insulin-induced paralysis (in males). Horses afflicted with the disorder can suddenly collapse, despite an impressive physique. In the past three years, these clinically defined disorders have been shown to share a common etiology: subtle defects of ion channels in the muscle-fiber membrane. Although the specific ion channel involved varies depending on the disease, most patients have single amino acid changes in the channel proteins, with both normal and mutant channels present in each muscle fiber. For each patient, we can now establish a precise molecular diagnosis in the face of overlapping clinical symptoms and begin specific pharmacological treatment based on the primary problem. These studies have also provided insight into basic muscle biology and emphasize the careful regulation of ions in muscle excitation.
Hoffman
E P
EP
Department of Molecular Genetics, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
D000818:Animals; D015220:Calcium Channels / Q000235:genetics* / Q000502:physiology; D018118:Chloride Channels / Q000235:genetics* / Q000502:physiology; D006734:Horse Diseases / Q000235:genetics / Q000503:physiopathology; D006736:Horses; D006801:Humans; D008564:Membrane Potentials / Q000235:genetics / Q000502:physiology; D008967:Molecular Biology; D018482:Muscle, Skeletal / Q000503:physiopathology; D009222:Myotonia / Q000235:genetics* / Q000503:physiopathology / Q000662:veterinary; D010245:Paralyses, Familial Periodic / Q000235:genetics* / Q000503:physiopathology / Q000662:veterinary; D015222:Sodium Channels / Q000235:genetics* / Q000502:physiology
D015220:Calcium Channels; D018118:Chloride Channels; D015222:Sodium Channels