PROPERTIES OF HUMAN GLIAL-CELLS ASSOCIATED WITH EPILEPTIC SEIZURE FOCI

We studied physiological properties of glial cells from acute slices o f biopsies from patients operated for intractable mesio-temporal lobe epilepsy using whole-cell patch-clamp recordings. Cells were filled wi th Lucifer Yellow (LY) during recordings to allow morphological recons truction and immunohistochemical cell identification. Seizure-associat ed astrocytes had complex, arborized, highly branched processes giving them a stellate appearance, and cells stained intensely for the inter mediate filament GFAP as previously reported for 'reactive' astrocytes . GFAP-positive astrocytes from epilepsy biopsies consistently express ed voltage-activated, TTX-sensitive Na+ channels that showed fast acti vation and inactivation kinetics. Unlike comparison astrocytes, derive d from tissues that were not associated with seizure foci, these astro cytes expressed Na+ channels at densities sufficient to generate slow action potentials (spikes) in current clamp studies. In these cells, t he ratio of Na+ to K+ conductance was consistently 3-4-fold higher tha n 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 rect ifying K+ currents, which in normal astrocytes are implicated in the c ontrol of extracellular K+ levels. These results suggest that astrocyt es surrounding seizure foci differ in morphological and physiological properties, and that glial K+ buffering could be impaired at the seizu re focus, thus contributing to the pathophysiology of seizures. (C) 19 98 Elsevier Science B.V. All rights reserved.