Properties of human glial cells associated with epileptic seizure foci.
We studied physiological properties of glial cells from acute slices of biopsies from patients operated for intractable mesio-temporal lobe epilepsy using whole-cell patch-clamp recordings. Cells were filled with Lucifer Yellow (LY) during recordings to allow morphological reconstruction and immunohistochemical cell identification. Seizure-associated astrocytes had complex, arborized, highly branched processes giving them a stellate appearance, and cells stained intensely for the intermediate filament GFAP as previously reported for 'reactive' astrocytes. GFAP-positive astrocytes from epilepsy biopsies consistently expressed voltage-activated, TTX-sensitive Na+ channels that showed fast activation and inactivation kinetics. Unlike comparison astrocytes, derived from tissues that were not associated with seizure foci, these astrocytes expressed Na+ channels at densities sufficient to generate slow action potentials (spikes) in current clamp studies. In these cells, the ratio of Na+ to K+ conductance was consistently 3-4-fold higher than in comparison human or control rat astrocytes. Four of 17 astrocytes from epilepsy patients versus 14/14 from control rat hippocampus and four of five in comparison human tissue showed a lack of inwardly rectifying K+ currents, which in normal astrocytes are implicated in the control of extracellular K+ levels. These results suggest that astrocytes surrounding seizure foci differ in morphological and physiological properties, and that glial K+ buffering could be impaired at the seizure focus, thus contributing to the pathophysiology of seizures.
Department of Neurobiology, University of Alabama at Birmingham, 35294, USA.
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Bordey
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Sontheimer
D000328:Adult; D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000502:physiology; D004828:Epilepsies, Partial / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D004833:Epilepsy, Temporal Lobe / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials; D008875:Middle Aged; D009457:Neuroglia / Q000473:pathology / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D012016:Reference Values; D015222:Sodium Channels / Q000502:physiology; D013702:Temporal Lobe / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery
D005904:Glial Fibrillary Acidic Protein; D015221:Potassium Channels; D015222:Sodium Channels