title: Evidence that compromised K+ spatial buffering contributes to the epileptogenic effect of mutations in the human Kir4.1 gene (KCNJ10).
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.
authors: Centre for Molecular Biology and Neuroscience, Letten Centre, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors: Nadia Nabil
authors: NN
authors: Haj-Yasein
authors: Vidar
authors: V
authors: Jensen
authors: Gry Fluge
authors: GF
authors: Vindedal
authors: Georg Andreas
authors: GA
authors: Gundersen
authors: Arne
authors: A
authors: Klungland
authors: Ole Petter
authors: OP
authors: Ottersen
authors: Oivind
authors: O
authors: Hvalby
authors: Erlend Arnulf
authors: EA
authors: Nagelhus
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics; D015153:Blotting, Western; D002021:Buffers; D004558:Electric Stimulation; D004586:Electrophoresis; D004827:Epilepsy / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D006046:Gold; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron; D009154:Mutation / Q000235:genetics / Q000502:physiology; D009457:Neuroglia / Q000201:enzymology; D011188:Potassium / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D012640:Seizures / Q000235:genetics / Q000503:physiopathology; D000098854:Kcnj10 Channel
chemical_list: D051401:Aquaporin 4; D002021:Buffers; D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; D006046:Gold; D011188:Potassium