Voltage-gated potassium channel KCNV2 (Kv8.2) contributes to epilepsy susceptibility

Benjamin S. Jorge, Courtney M. Campbell, Alison R. Miller, Elizabeth D. Rutter, Christina A. Gurnett, Carlos G. Vanoye, Alfred L. George, Jennifer A. Kearney

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Mutations in voltage-gated ion channels are responsible for several types of epilepsy. Genetic epilepsies often exhibit variable severity in individuals with the same mutation, which may be due to variation in genetic modifiers. The Scn2aQ54 transgenic mouse model has a sodium channel mutation and exhibits epilepsy with strain-dependent severity. We previously mapped modifier loci that influence Scn2aQ54 phenotype severity and identified Kcnv2, encoding the voltage-gated potassium channel subunit Kv8.2, as a candidate modifier. In this study, we demonstrate a threefold increase in hippocampal Kcnv2 expression associated with more severe epilepsy. In vivo exacerbation of the phenotype by Kcnv2 transgenes supports its identification as an epilepsy modifier. The contribution of KCNV2 to human epilepsy susceptibility is supported by identification of two nonsynonymous variants in epilepsy patients that alter function of Kv2.1/Kv8.2 heterotetrameric potassium channels. Our results demonstrate that altered potassium subunit function influences epilepsy susceptibility and implicate Kcnv2 as an epilepsy gene.

Original languageEnglish (US)
Pages (from-to)5443-5448
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number13
DOIs
StatePublished - Mar 29 2011

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Voltage-Gated Potassium Channels
Epilepsy
Mutation
Phenotype
Sodium Channels
Potassium Channels
Transgenes
Ion Channels
Transgenic Mice
Potassium

ASJC Scopus subject areas

  • General

Cite this

Jorge, Benjamin S. ; Campbell, Courtney M. ; Miller, Alison R. ; Rutter, Elizabeth D. ; Gurnett, Christina A. ; Vanoye, Carlos G. ; George, Alfred L. ; Kearney, Jennifer A. / Voltage-gated potassium channel KCNV2 (Kv8.2) contributes to epilepsy susceptibility. In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 13. pp. 5443-5448.
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Voltage-gated potassium channel KCNV2 (Kv8.2) contributes to epilepsy susceptibility. / Jorge, Benjamin S.; Campbell, Courtney M.; Miller, Alison R.; Rutter, Elizabeth D.; Gurnett, Christina A.; Vanoye, Carlos G.; George, Alfred L.; Kearney, Jennifer A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 13, 29.03.2011, p. 5443-5448.

Research output: Contribution to journalArticle

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AU - Campbell, Courtney M.

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AU - Gurnett, Christina A.

AU - Vanoye, Carlos G.

AU - George, Alfred L.

AU - Kearney, Jennifer A.

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