Properties of a delayed rectifier potassium current in dentate granule cells isolated from the hippocampus of patients with chronic temporal lobe epilepsy

Purpose: Properties of potassium outward currents were investigated in human hippocampal dentate gyrus granule cells from 11 hippocampal specimens obtained from patients with temporal lobe epilepsy (TLE) during resective surgery. Methods: Dentate granule cells were isolated enzymatically and outward currents analyzed by using the whole cell configuration of the patch-clamp method. Hippocampal specimens were classified neuropathologically with respect to severe segmental cell loss, gliosis, and axonal sprouting (Ammon's horn sclerosis, AHS), or the presence of a focal lesion in the adjacent temporal lobe. Results: A delayed rectifier outward current (I-K), but not an A-type potassium current (I-A) or inwardly rectifying potassium currents, was observed in all cells. The average current density of I-K, the time-dependent decay of I-K, and the resting membrane characteristics were not significantly different between patients with and without AHS. The voltage of half-maximal activation V-1/2(act) was 5.4 +/- 1.8 mV in AHS compared with -2.9 +/- 1.8 mV in lesion-associated epilepsy (NS). In contrast, V-1/2(inact) was shifted in a hyperpolarizing direction in AHS (-67.7 +/- 0.6 mV) compared with that in hippocampi not showing AHS (-47.7 +/- 2.6 mV; p = 0.0017). Conclusions: The altered steady-state voltage-dependence of I-K may result in abnormal excitability of dentate granule cells in AHS and exert a marked influence on input-output properties of the dentate gyrus.