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Kcna1-mutant rats dominantly display myokymia, neuromyotonia and spontaneous epileptic seizures.

Authors: Ishida, S  Sakamoto, Y  Nishio, T  Baulac, S  Kuwamura, M  Ohno, Y  Takizawa, A  Kaneko, S  Serikawa, T  Mashimo, T 
Citation: Ishida S, etal., Brain Res. 2012 Jan 30;1435:154-66. doi: 10.1016/j.brainres.2011.11.023. Epub 2011 Nov 13.
Pubmed: (View Article at PubMed) PMID:22206926
DOI: Full-text: DOI:10.1016/j.brainres.2011.11.023

Mutations in the KCNA1 gene, which encodes for the alpha subunit of the voltage-gated potassium channel Kv1.1, cause episodic ataxia type 1 (EA1). EA1 is a dominant human neurological disorder characterized by variable phenotypes of brief episodes of ataxia, myokymia, neuromyotonia, and associated epilepsy. Animal models for EA1 include Kcna1-deficient mice, which recessively display severe seizures and die prematurely, and V408A-knock-in mice, which dominantly exhibit stress-induced loss of motor coordination. In the present study, we have identified an N-ethyl-N-nitrosourea-mutagenized rat, named autosomal dominant myokymia and seizures (ADMS), with a missense mutation (S309T) in the voltage-sensor domain, S4, of the Kcna1 gene. ADMS rats dominantly exhibited myokymia, neuromyotonia and generalized tonic-clonic seizures. They also showed cold stress-induced tremor, neuromyotonia, and motor incoordination. Expression studies of homomeric and heteromeric Kv1.1 channels in HEK cells and Xenopus oocytes, showed that, although S309T channels are transferred to the cell membrane surface, they remained non-functional in terms of their biophysical properties, suggesting a dominant-negative effect of the S309T mutation on potassium channel function. ADMS rats provide a new model, distinct from previously reported mouse models, for studying the diverse functions of Kv1.1 in vivo, as well as for understanding the pathology of EA1.

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CRRD Object Information
CRRD ID: 10047237
Created: 2015-07-11
Species: All species
Last Modified: 2015-07-11
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.