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Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder.

Publication ,  Journal Article
Du, W; Bautista, JF; Yang, H; Diez-Sampedro, A; You, S-A; Wang, L; Kotagal, P; Lüders, HO; Shi, J; Cui, J; Richerson, GB; Wang, QK
Published in: Nat Genet
July 2005

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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Published In

Nat Genet

DOI

ISSN

1061-4036

Publication Date

July 2005

Volume

37

Issue

7

Start / End Page

733 / 738

Location

United States

Related Subject Headings

  • Xenopus laevis
  • Protein Subunits
  • Potassium Channels, Calcium-Activated
  • Pedigree
  • Oocytes
  • Mutation
  • Molecular Sequence Data
  • Large-Conductance Calcium-Activated Potassium Channels
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
  • Humans
 

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Du, W., Bautista, J. F., Yang, H., Diez-Sampedro, A., You, S.-A., Wang, L., … Wang, Q. K. (2005). Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder. Nat Genet, 37(7), 733–738. https://doi.org/10.1038/ng1585
Du, Wei, Jocelyn F. Bautista, Huanghe Yang, Ana Diez-Sampedro, Sun-Ah You, Lejin Wang, Prakash Kotagal, et al. “Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder.Nat Genet 37, no. 7 (July 2005): 733–38. https://doi.org/10.1038/ng1585.
Du W, Bautista JF, Yang H, Diez-Sampedro A, You S-A, Wang L, et al. Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder. Nat Genet. 2005 Jul;37(7):733–8.
Du, Wei, et al. “Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder.Nat Genet, vol. 37, no. 7, July 2005, pp. 733–38. Pubmed, doi:10.1038/ng1585.
Du W, Bautista JF, Yang H, Diez-Sampedro A, You S-A, Wang L, Kotagal P, Lüders HO, Shi J, Cui J, Richerson GB, Wang QK. Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder. Nat Genet. 2005 Jul;37(7):733–738.

Published In

Nat Genet

DOI

ISSN

1061-4036

Publication Date

July 2005

Volume

37

Issue

7

Start / End Page

733 / 738

Location

United States

Related Subject Headings

  • Xenopus laevis
  • Protein Subunits
  • Potassium Channels, Calcium-Activated
  • Pedigree
  • Oocytes
  • Mutation
  • Molecular Sequence Data
  • Large-Conductance Calcium-Activated Potassium Channels
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
  • Humans