title: Loss of perivascular Kir4.1 potassium channels in the sclerotic hippocampus of patients with mesial temporal lobe epilepsy.
abstract: Recent experimental data in mice have shown that the inwardly rectifying K channel Kir4.1 mediates K spatial buffering in the hippocampus. Here we used immunohistochemistry to examine the distribution of Kir4.1 in hippocampi from patients with medication-refractory temporal lobe epilepsy. The selectivity of the antibody was confirmed in mice with a glial conditional deletion of the gene encoding Kir4.1. These mice showed a complete loss of labeled cells, indicating that Kir4.1 is restricted to glia. In human cases, Kir4.1 immunoreactivity observed in cells morphologically consistent with astrocytes was significantly reduced in 12 patients with hippocampal sclerosis versus 11 patients without sclerosis and 4 normal autopsy controls. Loss of astrocytic Kir4.1 immunoreactivity was most pronounced around vessels and was restricted to gliotic areas. Loss of Kir4.1 expression was associated with loss of dystrophin and α-syntrophin, but not with loss of β-dystroglycan, suggesting partial disruption of the dystrophin-associated protein complex. The changes identified in patients with hippocampal sclerosis likely interfere with K homeostasis and may contribute to the epileptogenicity of the sclerotic hippocampus.
authors.affiliation: Department of Neurology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Kjell
authors.initials: K
authors.lastname: Heuser
authors.forename: Tore
authors.initials: T
authors.lastname: Eid
authors.forename: Fredrik
authors.initials: F
authors.lastname: Lauritzen
authors.forename: Anna E
authors.initials: AE
authors.lastname: Thoren
authors.forename: Gry F
authors.initials: GF
authors.lastname: Vindedal
authors.forename: Erik
authors.initials: E
authors.lastname: Taubøll
authors.forename: Leif
authors.initials: L
authors.lastname: Gjerstad
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Spencer
authors.forename: Ole P
authors.initials: OP
authors.lastname: Ottersen
authors.forename: Erlend A
authors.initials: EA
authors.lastname: Nagelhus
authors.forename: Nihal C
authors.initials: NC
authors.lastname: de Lanerolle
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002648:Child; D049030:Dystroglycans / Q000378:metabolism; D016189:Dystrophin / Q000378:metabolism; D004833:Epilepsy, Temporal Lobe / Q000150:complications / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D012598:Sclerosis / Q000209:etiology* / Q000473:pathology; D055815:Young Adult; D000098854:Kcnj10 Channel
chemical_list: D002135:Calcium-Binding Proteins; D016189:Dystrophin; D000098854:Kcnj10 Channel; D008565:Membrane Proteins; D009124:Muscle Proteins; D024661:Potassium Channels, Inwardly Rectifying; C091825:syntrophin alpha1; D049030:Dystroglycans