title: Chronic dysfunction of astrocytic inwardly rectifying K+ channels specific to the neocortical epileptic focus after fluid percussion injury in the rat.
abstract: Astrocytic inwardly rectifying K(+) currents (I(KIR)) have an important role in extracellular K(+) homeostasis, which influences neuronal excitability, and serum extravasation has been linked to impaired K(IR)-mediated K(+) buffering and chronic hyperexcitability. Head injury induces acute impairment in astroglial membrane I(KIR) and impaired K(+) buffering in the rat hippocampus, but chronic spontaneous seizures appear in the perilesional neocortex--not the hippocampus--in the early weeks to months after injury. Thus we examined astrocytic K(IR) channel pathophysiology in both neocortex and hippocampus after rostral parasaggital fluid percussion injury (rpFPI). rpFPI induced greater acute serum extravasation and metabolic impairment in the perilesional neocortex than in the underlying hippocampus, and in situ whole cell recordings showed a greater acute loss of astrocytic I(KIR) in neocortex than hippocampus. I(KIR) loss persisted through 1 mo after injury only in the neocortical epileptic focus, but fully recovered in the hippocampus that did not generate chronic seizures. Neocortical cell-attached recordings showed no loss or an increase of I(KIR) in astrocytic somata. Confocal imaging showed depletion of KIR4.1 immunoreactivity especially in processes--not somata--of neocortical astrocytes, whereas hippocampal astrocytes appeared normal. In naïve animals, intracortical infusion of serum, devoid of coagulation-mediating thrombin activity, reproduces the effects of rpFPI both in vivo and at the cellular level. In vivo serum infusion induces partial seizures similar to those induced by rpFPI, whereas bath-applied serum, but not dialyzed albumin, rapidly silenced astrocytic K(IR) membrane currents in whole cell and cell-attached patch-clamp recordings in situ. Thus both acute impairment in astrocytic I(KIR) and chronic spontaneous seizures typical of rpFPI are reproduced by serum extravasation, whereas the chronic impairment in astroglial I(KIR) is specific to the neocortex that develops the epileptic focus.
authors.affiliation: Department of Neurological Surgery, University of Washington, School of Medicine, Seattle, USA.
authors.forename: Tessandra H
authors.initials: TH
authors.lastname: Stewart
authors.forename: Clifford L
authors.initials: CL
authors.lastname: Eastman
authors.forename: Peter A
authors.initials: PA
authors.lastname: Groblewski
authors.forename: Jason S
authors.initials: JS
authors.lastname: Fender
authors.forename: Derek R
authors.initials: DR
authors.lastname: Verley
authors.forename: David G
authors.initials: DG
authors.lastname: Cook
authors.forename: Raimondo
authors.initials: R
authors.lastname: D'Ambrosio
mesh_terms: D000244:Adenosine Diphosphate / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D001930:Brain Injuries / Q000150:complications / Q000503:physiopathology*; D002851:Chromatography, High Pressure Liquid; D004569:Electroencephalography; D004828:Epilepsies, Partial / Q000209:etiology / Q000503:physiopathology*; D005122:Exudates and Transudates; D008297:Male; D018613:Microscopy, Confocal; D019579:Neocortex / Q000293:injuries* / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044967:Serum; D013917:Thrombin / Q000032:analysis; D014741:Video Recording; D000098854:Kcnj10 Channel
chemical_list: D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D013917:Thrombin