Increased leak conductance in dentate gyrus granule cells of temporal lobe epilepsy patients with Ammon’s horn sclerosis

Abstract

Temporal lobe epilepsy (TLE) is often associated with Ammon's horn sclerosis (AHS) characterized by hippocampal cell death and dentate gyrus granule cell dispersion (GCD). Granule cells survive AHS and have been proposed to be hyperexcitable in TLE. Here we studied whether the passive excitability of granule cells correlates with the severity of AHS. We analyzed the passive membrane properties of identified granule cells using patch-clamp recordings in acute tissue slices obtained from TLE surgery. Independent Wyler grading and GCD measurements were used to assess the severity of AHS. The input resistances and membrane time constants of granule cells were reduced in high-grade versus low-grade AHS samples and negatively correlated with the degree of GCD. Granule cells possessed large Ba(2+)-sensitive, inwardly rectifying K(+) conductances. The increased leak conductance, likely mediated by K(+) channels, does not argue for an increased excitability of granule cells but rather points to a neuroprotective mechanism in the sclerotic focus in TLE.