Astrocytic regulation of the recovery of extracellular potassium after seizures in vivo.
Glial cells are believed to play a major role in the regulation of the extracellular potassium concentration ([K+]o), particularly when the [K+]o is increased. Using ion-selective electrodes, we compared the [K+]o changes in the dentate gyrus of urethane-anaesthetized adult rats in the presence of reactive astrocytes and after reduction of glial function. The regulation of [K+]o in the dentate gyrus was determined by measuring the ceiling level of [K+]o and the half-time of recovery of [K+]o during and after seizures produced by 20 Hz trains of stimulation to the angular bundle. Reactive astrocytes were induced by repeated seizures and their presence was confirmed by a qualitative increase in glial fibrillary acidic protein (GFAP) and vimentin immunoreactivity. To inhibit glial function, fluorocitrate (FC), a reversible metabolic inhibitor, or alpha-aminoadipate (alpha-AA), an irreversible toxin, was injected into the dentate gyrus region, and the regulation of [K+]o was monitored for 8 h or 2 days later, respectively. After alpha-aminoadipate, loss of astrocytes in the dentate gyrus was demonstrated by loss of staining for GFAP. In the presence of reactive astrocytes there was no significant change in the peak [K+]o during seizures or the half-time of recovery of [K+]o after seizures compared to control animals. alpha-Aminoadipate significantly slowed the rate of recovery of [K+]o, but did not change the ceiling [K+]o. Fluorocitrate reversibly decreased the ceiling [K+]o, but also slowed the rate of recovery of [K+]o. Overall our results suggest that normal glial function is required for the recovery of elevated [K+]o after seizures in vivo.
Xiong
Z Q
ZQ
Department of Pharmacology and Division of Neurosciences, Baylor College of Medicine, Houston, TX 77030, USA.
Stringer
J L
JL
D015074:2-Aminoadipic Acid / Q000494:pharmacology; D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D002951:Citrates / Q000494:pharmacology; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism; D004594:Electrophysiology; D004827:Epilepsy / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D008297:Male; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014746:Vimentin / Q000032:analysis
D002951:Citrates; D018691:Excitatory Amino Acid Antagonists; D005904:Glial Fibrillary Acidic Protein; D014746:Vimentin; D015074:2-Aminoadipic Acid; C007744:fluorocitrate; D011188:Potassium