title: Astrocytes in the hippocampus of patients with temporal lobe epilepsy display changes in potassium conductances.
abstract: Functional properties of astrocytes were investigated with the patch-clamp technique in acute hippocampal brain slices obtained from surgical specimens of patients suffering from pharmaco-resistant temporal lobe epilepsy (TLE). In patients with significant neuronal cell loss, i.e. Ammon's horn sclerosis, the glial current patterns resembled properties characteristic of immature astrocytes in the murine or rat hippocampus. Depolarizing voltage steps activated delayed rectifier and transient K+ currents as well as tetrodotoxin-sensitive Na+ currents in all astrocytes analysed in the sclerotic human tissue. Hyperpolarizing voltages elicited inward rectifier currents that inactivated at membrane potentials negative to -130 mV. Comparative recordings were performed in astrocytes from patients with lesion-associated TLE that lacked significant histopathological hippocampal alterations. These cells displayed stronger inward rectification. To obtain a quantitative measure, current densities were calculated and the ratio of inward to outward K+ conductances was determined. Both values were significantly smaller in astrocytes from the sclerotic group compared with lesion-associated TLE. During normal development of rodent brain, astroglial inward rectification gradually increases. It thus appears reasonable to suggest that astrocytes in human sclerotic tissue return to an immature current pattern. Reduced astroglial inward rectification in conjunction with seizure-induced shrinkage of the extracellular space may lead to impaired spatial K+ buffering. This will result in stronger and prolonged depolarization of glial cells and neurons in response to activity-dependent K+ release, and may thus contribute to seizure generation in this particular condition of human TLE.
authors.affiliation: Experimental Neurobiology, Department of Neurosurgery, University of Bonn, Sigmund-Freud-Str. 25, 53125 Bonn, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Hinterkeuser
authors.forename: W
authors.initials: W
authors.lastname: Schröder
authors.forename: G
authors.initials: G
authors.lastname: Hager
authors.forename: G
authors.initials: G
authors.lastname: Seifert
authors.forename: I
authors.initials: I
authors.lastname: Blümcke
authors.forename: C E
authors.initials: CE
authors.lastname: Elger
authors.forename: J
authors.initials: J
authors.lastname: Schramm
authors.forename: C
authors.initials: C
authors.lastname: Steinhäuser
mesh_terms: D000328:Adult; D001253:Astrocytes / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009414:Nerve Growth Factors / Q000235:genetics; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger / Q000032:analysis; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D012598:Sclerosis; D012964:Sodium / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D002135:Calcium-Binding Proteins; D009414:Nerve Growth Factors; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D013779:Tetrodotoxin; D012964:Sodium; D011188:Potassium