Journal article
Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder
Nature genetics, Vol.37(7), pp.733-738
07/2005
DOI: 10.1038/ng1585
PMID: 15937479
Abstract
The large conductance calcium-sensitive potassium (BK) channel is widely expressed in many organs and tissues, but its in vivo physiological functions have not been fully defined. Here we report a genetic locus associated with a human syndrome of coexistent generalized epilepsy and paroxysmal dyskinesia on chromosome 10q22 and show that a mutation of the α subunit of the BK channel causes this syndrome. The mutant BK channel had a markedly greater macroscopic current. Single-channel recordings showed an increase in open-channel probability due to a three- to fivefold increase in Ca2+ sensitivity. We propose that enhancement of BK channels in vivo leads to increased excitability by inducing rapid repolarization of action potentials, resulting in generalized epilepsy and paroxysmal dyskinesia by allowing neurons to fire at a faster rate. These results identify a gene that is mutated in generalized epilepsy and paroxysmal dyskinesia and have implications for the pathogenesis of human epilepsy, the neurophysiology of paroxysmal movement disorders and the role of BK channels in neurological disease.
Details
- Title: Subtitle
- Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder
- Creators
- Qing K Wang - Center for Molecular Genetics, Department of Molecular Cardiology, Lerner Research Institute; Center for Cardiovascular Genetics, Department of Cardiovascular Medicine, The Cleveland Clinic Foundation; and Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine; Case Western Reserve University Department of Biological, Geological, and Environmental Science, Cleveland State University Huazhong University of Science and Technology Human Genome Research CenterJingyi Shi - Department of Biomedical Engineering, Washington UniversityAna Diez-SampedroLejin Wang - Center for Molecular Genetics, Department of Molecular Cardiology, Lerner Research Institute; Center for Cardiovascular Genetics, Department of Cardiovascular Medicine, The Cleveland Clinic Foundation; and Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine; Case Western Reserve UniversityPrakash Kotagal - Department of Neurology, The Cleveland Clinic FoundationJianmin Cui - Department of Biomedical Engineering, Washington UniversityHuanghe Yang - Department of Biomedical Engineering, Washington UniversityWei Du - Center for Molecular Genetics, Department of Molecular Cardiology, Lerner Research Institute; Center for Cardiovascular Genetics, Department of Cardiovascular Medicine, The Cleveland Clinic Foundation; and Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine; Case Western Reserve University Department of Biological, Geological, and Environmental Science, Cleveland State UniversityJocelyn F Bautista - Department of Neurology, The Cleveland Clinic Foundation Department of Epidemiology and Biostatistics, Case Western Reserve UniversityGeorge B Richerson - VAMCSun-Ah You - Center for Molecular Genetics, Department of Molecular Cardiology, Lerner Research Institute; Center for Cardiovascular Genetics, Department of Cardiovascular Medicine, The Cleveland Clinic Foundation; and Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine; Case Western Reserve UniversityHans O Lüders - Department of Neurology, The Cleveland Clinic Foundation
- Resource Type
- Journal article
- Publication Details
- Nature genetics, Vol.37(7), pp.733-738
- DOI
- 10.1038/ng1585
- PMID
- 15937479
- ISSN
- 1061-4036
- eISSN
- 1546-1718
- Language
- English
- Date published
- 07/2005
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Neurosurgery
- Record Identifier
- 9984020648002771
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