Astrocytes in the hippocampus of patients with temporal lobe epilepsy display changes in potassium conductances

Functional properties of astrocytes were investigated with the patch-clamp technique in acute hippocampal brain slices obtained from surgical specimen s of patients suffering from pharmaco-resistant temporal robe epilepsy (TLE ). in patients with significant neuronal cell loss, i.e. Ammon's horn scler osis, the glial current patterns resembled properties characteristic of imm ature astrocytes in the murine or rat hippocampus. Depolarizing voltage ste ps activated delayed rectifier and transient K+ currents as well as tetrodo toxin-sensitive Na+ currents in all astrocytes analysed in the sclerotic hu man tissue. Hyperpolarizing voltages elicited inward rectifier currents tha t inactivated at membrane potentials negative to -130 mV. Comparative recor dings were performed in astrocytes from patients with lesion-associated TLE that lacked significant histopathological hippocampal alterations. These c ells displayed stronger inward rectification. To obtain a quantitative meas ure, current densities were calculated and the ratio of inward to outward K + conductances was determined. Both values were significantly smaller in as trocytes 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 as troglial 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 ne urons in response to activity-dependent K+ release, and may thus contribute to seizure generation in this particular condition of human TLE.