Evidence that compromised K+ spatial buffering contributes to the epileptogenic effect of mutations in the human kir4.1 gene (KCNJ10)
✍ Scribed by Nadia Nabil Haj-Yasein; Vidar Jensen; Gry Fluge Vindedal; Georg Andreas Gundersen; Arne Klungland; Ole Petter Ottersen; Øivind Hvalby; Erlend Arnulf Nagelhus
- Book ID
- 102848025
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 995 KB
- Volume
- 59
- Category
- Article
- ISSN
- 0894-1491
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✦ Synopsis
Abstract
Mutations in the human Kir4.1 potassium channel gene (KCNJ10) are associated with epilepsy. Using a mouse model with glia‐specific deletion of Kcnj10, we have explored the mechanistic underpinning of the epilepsy phenotype. The gene deletion was shown to delay K^+^ clearance after synaptic activation in stratum radiatum of hippocampal slices. The activity‐dependent changes in extracellular space volume did not differ between Kcnj10 mutant and wild‐type mice, indicating that the Kcnj10 gene product Kir4.1 mediates osmotically neutral K^+^ clearance. Combined, our K^+^ and extracellular volume recordings indicate that compromised K^+^ spatial buffering in brain underlies the epilepsy phenotype associated with human KCNJ10 mutations. © 2011 Wiley‐Liss, Inc.