Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder.
Nat Genet
; 37(7): 733-8, 2005 Jul.
Article
en En
| MEDLINE
| ID: mdl-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 alpha 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 Ca(2+) 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.
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Banco de datos:
MEDLINE
Asunto principal:
Corea
/
Epilepsia Generalizada
/
Canales de Potasio Calcio-Activados
Tipo de estudio:
Diagnostic_studies
Límite:
Adolescent
/
Adult
/
Animals
/
Child, preschool
/
Female
/
Humans
Idioma:
En
Revista:
Nat Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos